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THE   SCIENCE    SERIES 

Edited  by  Edward  Lee  Thorndike,  Ph.D.,  and 
F.  E.  Beddard,  M.A.,  F.R.S. 


1.  The  study  of  Man.     By  A.  C.  Haddou. 

2.  The  Qroundwork  of  Science.      By  St.  Geo^.  e.  Mivart. 

3.  Rivers  of  North  America.    By  Israel  C.  Russell. 

4.  Earth  Sculpture,  or  ;  The  Origin  of  Land  Forms.    By  James 

Geikie. 

5.  Volcanoes  ;  Their  Structure  and  Significance.     By  T.   G. 

BONNEY. 

6.  Bacteria.      By  George  Newman. 

7.  A  Book  of  Whales.      By  F.  E.  BtDDARo. 

8.  Comparative  Physiology  of  the  Brain,  etc.   By  Jacques  Loer. 

9.  The  Stars.     By  Simon  Newcomb. 

10.  The  Basis  of  Social  Relations.      By  Daniel  G.  Brinton. 

11.  Experimer>-s  on  Animals.      By  Stephen  Paget. 

12.  Infection  and  Immunity.      By  George  M.  Sternberg. 

13.  Fatigue.      By  A.  Mosso. 

14.  Earthquakes.     By  Clarence  E.  Dutton. 

15.  The  Nature  of  Man.     By  Elie  Metchnikoff. 

16.  Nervous  and  Mental  Hygiene  in  Health  and   Disease.     By 

August  Forel. 

17.  The  Prolongation  of  Life.    By  Elie  Metchnikoff. 

18.  The  Solar  System.      By  Charles  Lake  Poor. 
ig.  Heredity.     By  J.  Arthur  Thompson,  M.A. 

20.  Climate.      By  Robert  DeCoukcy  Ward. 

21.  Age,  Growth,  and  Death.    By  Charles  S.  Minot. 

i2.  The  Interpretation  of  Nature.      By  C.  Lloyd  Morgan. 

23.  Mosquito  Life.    By  Evelvn  Groesbeeck Mitchell. 

24.  Thinking,  Feeling,  Doing.     By  E.  W.  Scripture. 


J^or  list  of  works  in  preparation  see  end  of  this  volume. 


TLbc  Science  Series 

EDITED    BY 

JE^)war^  Xee  ■JEboiiiMfte,  |pb.S>. 

AND 

3f .  E.  36eB6ar6,  m.U.,  jf.tR.S, 


The   Problem  of 
Age,  Growth,  and   Death 


The  Problem 

of 

Age,  Growth,  and  Death 

A  Study  of  Cytomorphosis 

Based  on  Lectures  at  the  Lowell  Institute 
March,  1907 


By 

Charles  S.  Minot 

LL.D.   (Yale,   Toronto),   D.Sc.   (Oxford) 

James   Stillman    Professor    of   Comparative   Anatomy    in    the   Harvard    Medical     School 

President  of  the  Boston  Society  of  Natural  History 


Illustrated 


G.    P.   Putnam's  Sons 

New     York     and      London 
Zbc     IRnicl^erbocfier    piess 

1908 


Copyright,  igo8 

BY 

CHARLES  S.  MINOT 


Ube  1kn(cfterbocf?ec  iprcss,  mew  KorS 


ANGELO  iNIOSSO 

SENATOR    OF    THE    KINGDOM    OF    ITALY 

PROFESSOR    OF    PHYSIOLOGY    AT    THE    UNIVERSITY    OF    TURIN 

THIS    VOLUME   IS   DEDICATED 

BY   THE   AUTHOR 


CONTENTS 

PAGE 

INTRODUCTORY    LETTER    TO    SENATOR    MOSSO  .  .  .         vii 

CHAPTER  I 
THE    CONDITION    OF    OLD    AGE  ......  I 

CHAPTER  II 
CYTOMORPHOSIS:    THE    CELLULAR    CHANGES    OF    AGE       .  .  38 

CHAPTER  III  ,'J 

THE    RATE    OF    GROWTH  .......  86 

CHAPTER  IV 
DIFFERENTIATION    AND    REJUVENATION  ....       I3I 

CHAPTER  V 
REGENERATION    AND    DEATH  ......       169 

CHAPTER  VI 
THE    FOUR    LAWS    OF    AGE        .......       2x8 

APPENDIX  I 
GROWTH    OF    RABBITS     ....... 


APPENDIX  II 
GROWTH    OF    CHICKENS 


253 


258 


APPENDIX  III 
DEATH    OF    PROTOZOA     ........       262 


vi  -  CONTENTS 

PAGE 

APPENDIX  IV 
LONGEVITY    OF    ANIMALS .       266 

APPENDIX  V 
THEORY    OF    LIFE    . 267 

APPENDIX  VI 
THE    AGE-RECKONER        ........       273 

INDEX 275 


ILLUSTRATIONS 

FIGURE 

1.  Two  Human  Vertebral  Columns 

2.  Photograph  of  Chevreul       .... 

3.  Photograph  from  a  Child  at  Birth 
4A.    ^  f  Child  at  Birth 
4B.     >•  Ribs  and  Sternum  -<  Child  at  Seven  Years 
4c.     J  V  Adult,  Thirty  Years 

5.  Section  of  the  Head  of  the  Thigh  Bone  of  a  Man 

6.  Section  of  the  Head  of  the  Thigh  Bone  of  a  Woman 

7.  Cells  from  the  Mouth  of  the  Salamander 

8.  Example  of  a  Syncytium      .  .  .  •         • 

9.  Three  Transverse  Sections  through  a  Rabbit  Embryo 

of  Seven  and  One-Half  Days 

10.  Portion  of  a  Transverse  Section  of  the  Spinal  Cord 

of  a  Human  Embryo  of  Four  Millimetres 

11.  Copy  of  Original  Figure  from  the  Memoir  of  Deiters 

12.  A  Large  Cell  from  the  Small  Brain  of  a  Man 

13.  Various  Kinds  of  Human  Nerve  Cells 

14.  Sections  of  Four  Sorts  of  Epithelium  . 

15.  To  Show  the  Orbital  Gland  of  a  Dog 

16.  Two  Sections  of  the  Pancreatic  Gland  of  a  Dog 

17.  Section  of  the  Human  Skin,  Made  so  that  the  Hairs 

are  Cut  Lengthwise         ..... 


9 

I  2 

40 
44 

46 


50 
51 
53 
55 
56 
58 

59 


viii  ILLUSTRATIONS 


i8.     Cross-Section  of  the  Root  of  a  Hair    . 

19,     Cross-Section    of     a     Lingual     Muscle    Fibre    of  the 
Moccasin  Snake     ...... 


61 


62 
62 

63 
66 


20.  Part  of  a  Muscle  Fibre  of  the  Human  Tongue    . 

21.  Section  of  a  Human  Retina  .... 

22.  Motor  Nerve  Cells  of  Various  Mammals 

23.  Group    of  Five   Nerve    Cells  from  the  First  Cervical 

Ganglion  of  a  Child  at  Birth  ....        68 

24.  Group    of   Four  Nerve   Cells   from  the  First  Cervical 

Ganglion  of  a  Man  Dying  of  Old  Age,  at  92  Years       69 

25.  Life  History  of  Blood  Corpuscles,  Rabbit  Embryos    .        78 

26.  Four  Tadpoles  of  the  European  Frog  ...        88 

27.  Curves  Showing  the  Growth  of  Boston  School  Children 

in  Height  and  Weight  .  .  .  .         .91 

28.  Curves  Showing  the   Daily   Percentage  Increments  in 

Weight  of  Male  Guinea- Pigs  ....        94 

29.  Curves  Showing  the   Daily  Percentage  Increments   in 

Weight  of  Female  Guinea-Pigs        ....       96 

30.  Curves  Showing  the  Length  of  Time  Required  to  Make 

Each  Successive   Increase  of  Ten    per    Cent,    in 
Weight  by  Male  Guinea-Pigs  .  ...       97 

3  r.  Curves  Showing  the  Length  of  Time  Required  to  Make 
Each  Successive  Increase  of  Ten  per  Cent,  in 
Weight  by  Female  Guinea-Pigs      ....       98 

32.  Curves   Showing   the   Growth   of  Man  from   Birth  to 

Maturity 99 

33.  Curves   Showing  the  Daily  Percentage   Increments  in 

Weight  by  Male  Chickens 10 1 

34.  Curves   Showing  the  Daily  Percentage  Increments  in 

Weight  by  Female  Chickens  ....      102 


ILLUSTRATIONS  ix 


35.     Curve  Showing   the    Daily  Percentage  Increments  in 
Weight  by  Male  Rabbits         .... 

2,6.     Curve  Showing    the   Daily  Percentage   Increments  in 
Weight  by  Female  Rabbits    .... 

37.  Yearly    Percentage    Increments   in  Weight  by   Boys, 

Reckoned  by  M.   Miihlmann 

38.  Yearly    Percentage   Increments    in   Weight    by  Boys 

after  H.  H.   Donaldson  .... 

39.  Yearly   Percentage    Increments   in  Weight   by    Girls 

Reckoned  by  M.  Miihlmann 

40.  Yearly  Percentage  Increments  in  Weight  by  Girls,  after 

H.    H.  Donaldson 

41.  Yearly  Percentage  Increments  in  Weight  by  Boys  and 

Girls 

42.  Ten  Stages  of  the  Developing  Chick 

43.  A  Chick  Removed  from  an  Egg  after  an  Incubation 

of  Ten  Days  and  Two  Hours 

44.  Fourteen  Stages  of  the  Developing  Rabbit 

45.  Percentage  Increments  up  to  Birth  in  Man  by  Lunar 

Months,  after  Miihlmann      .... 

46.  Cells  from  the  Mouth  of  the  Salamander     . 

47.  Three  Sections  through  a  Rabbit   Embyro  of  Seven 

and  One- Half  Days        ..... 

48A.   Entamoeba  Histolytica,  Highly  Magnified     . 
48B.  Preserved  Specimen  of  Entamceba  Histolytica 

49.  Tertian  Malarial  Parasite   ..... 

50.  Trypanosoma  Lewisi  ...... 

51.  Stentor  Coiruleus  ...... 

52.  Various  Kinds  of  Human  Nerve  Cells 


103 

105 
109 
no 

113 
114 

116 
119 

121 
123 

127 

136 

137 

139 
140 
141 
145 


ILLUSTRATIONS 


53.  Part  of  a  Human  Muscle  Fibre 

54.  Sections  from  an  Orbital  Gland  of  a  Dog    . 

55.  Diagram  of  Three  Cells  of  a  Salivary  Gland 

56.  Embryonic  Syncytium         ..... 

57.  Amoeba  Proteus  ...... 

58.  Sections  of  Three  Ova  in  very  Early  Stages 

59.  Progressive  Segmentation  of  the  Ovum 

60.  The  Segmentation  of  the  Ovum  of  Planorbis 

61.  Nuclei  from  Rabbit  Embryos      .... 

62.  Section  across  the    Posterior    Part    of    an     Embryo 

Dog-fish         ....... 

63.  Section  of  the  Cerebellum  of  a  Child  of  Thirteen  Days 

64A.  Section  of  a  Lens  of  the  Eye  of  a  Chick  of  Sixty-eight 
Hours'  Incubation         ...... 

64B.  Section  of  a  Lens  of  the  Eye  of  a  Chick  of  Ninety-six 
Hours'  Incubation         ...... 


65 

66 
67 
68 
69 

70 

71 

72 

73 


Section  of  a  Gland  of  the  Large  Intestine  of  an  Adult 
Cat        ......... 

Vignette  from  Trembley's  Classic  Memoir 

Stentor        ......... 

Striated  Muscle  Fibres  in  Process  of  Regeneration 

Section    of   the     Epithelial    Lining    of    the    Human 
CEsophagus  ....... 

Longitudinal  Sections  through  the  Antenna  of  Oniscus 

Section  through  a  Regenerating  Antenna  of  Oniscus 

Portion  of  the   Outer  Wall   of  a  Primitive   Muscular 
Segment  of  a  Cat  Embryo     ..... 

As;e-Reckoner  ....... 


PAGE 
147 

148 

148 

162 
164 

173 
176 

182 
187 

190 

190 

193 

198 
199 

203 
208 
209 

220 
272 


INTRODUCTORY  LETTER  TO  SENATOR 

MOSSO 

My  dear  Mosso  : 

It  is  now  over  a  third  of  a  century  since  we  were 
together  in  Leipzig  as  fellow-workers  in  the  laboratory 
of  Professor  Carl  Ludwig,  on  whom  we  look  back  as 
the  greatest  teacher  of  the  art  of  scientific  research 
whom  we  have  ever  known.  He  was  a  master  of 
both  the  two  great  methods  of  biological  study — 
observation  and  experiment.  From  him  we  learned  to 
regard  the  living  organism  as  an  apparatus,  of  which 
it  was  necessary  to  learn  both  the  construction  and 
the  working,  and  always  to  seek  the  explanation  of 
the  working  on  the  basis  of  the  construction.  Al- 
though we  have  followed  different  lines  of  inquiry, 
the  fundamental  conceptions  taught  us  by  Ludwig 
have  remained  dominant.  I  look  with  admiration 
upon  the  number  and  importance  of  your  scientific 
achievements.  The  pupil  has  proved  himself  worthy 
of  the  master,  and  has  taken  a  master's  place. 

You  will  find  in  this  volume,  I  trust,  evidence  of 
Ludwig's  continued  influence  upon  my  work,  and 
of  my  effort  to  follow  upon  a  lesser  scale  your  ex- 
ample.    The  years   which    have  passed   since   those 


xii   INTRODUCTORY  LETTER  TO  SENATOR  MOSSO 

delightful  student  days  have  brought  many  changes, 
and  have  transformed  us  into  members  of  the  older 
generation.  Therefore,  I  hope  that  you  will  regard 
the  dedication  of  this  volume  on  age  to  yourself  as  not 
inappropriate.  As  I  write  I  recall  our  parting  in  the 
forest  of  Fontainebleau,  our  meeting  on  the  glacier 
above  Zermatt,  our  paddling  together  in  a  canoe  on 
an  American  lake  along  the  edge  of  the  primeval 
forest,  and  many  other  experiences  which  we  have 
shared.  These  were  in  our  younger  days,  and  now 
our  interest  in  what  is  essential  among  the  effects  of 
age  has  a  personal  as  well  as  a  scientific  foundation. 

This  book  deals  with  a  series  of  important  biologi- 
cal problems,  yet  it  is  essentially  a  study  of  a  single 
phenomenon, — the  increase  in  the  amount  of  proto- 
plasm. The  increase  to  be  considered  is  not  that 
which  takes  place  at  large  in  the  body  of  the  growing 
animal,  but  that  which  takes  place  within  the  limits  of 
single  cells,  and  occurs  in  such  a  manner  that  the 
proportion  between  the  cell-body  and  the  nucleus  in 
volume,  or  bulk,  is  changed — the  cell-body  becoming 
relatively  either  larger  as  more  frequently  happens,  or 
smaller,  as  happens  in  special  cases. 

By  the  study  of  the  proportionate  volumes  of  the 
nucleus  and  the  cell-body  we  can  demonstrate,  I  be- 
lieve, certain  laws  governing  that  proportion,  and 
prove  that  the  variations  of  the  proportion  establish 
conditions  which  are  fundamental  to  the  correct  con- 
ception of  the  problems  of  growth,  differentiation, 
death,  and  sex.     It  is  my  endeavour,  by  following  the 


INTRODUCTORY  LETTER  TO  SENATOR  MOSSOxni 

precepts  of  Ludwig,  to  prove  the  existence  of  another 
set  of  correlations  between  the  structure  of  cells  and 
their  function,  which  hitherto  has  been  unrecognised. 
The  primary  correlation  of  the  variations  in  pro- 
portions, which  can  be  demonstrated,  is  with  the  age 
of  the  organism.  Accordingly,  the  investigation  of 
age  and  growth  occupies  a  large  share  of  the 
volume. 

The  subjects  discussed  in  this  book  have  received 
in  part,  hitherto,  relatively  little  attention  from  bio- 
logists, hence  the  scientific  literature  dealing  explicitly 
with  them  is  rather  scanty,  although  there  are  almost 
innumerable  observations  recorded  in  various  writ- 
ings, which  have  a  bearing  on  the  problems  to  be 
solved.  Under  these  circumstances  I  have  been 
forced,  necessarily,  to  rely  almost  exclusively  upon 
my  own  investigation  ;  accordingly,  the  conclusions 
have  a  personal  character  in  the  sense  that  they  have 
not  yet  been  subjected  to  the  critical  judgment  of  bio- 
logists. Nevertheless,  I  hope  that  they  will  commend 
themselves  to  you. 

My  own  active  interest  in  growth  as  a  biological 
problem  goes  back  twenty-nine  years,  when  I  pub- 
lished an  article  on  "  Growth  as  a  Function  of  Cells,"  ^ 
followed  by  another,  "On  Certain  Laws  of  Histo- 
logical Differentiation."^  These  two  papers,  however, 
were  of  a  somewhat  theoretical  character.  Feeline 
strongly  the  necessity,  which  I  should  feel  still  more 

'  Proceedings  Bosto7i  Soc.  Nat.  Hist.,  xx.,  igo  (1879). 
^  Ibidem,  p.  201. 


x\v  IXTRODUCTORY  LETTER  TO  SENATOR  MOSSO 

strongly  now,  of  getting  to  direct  facts,  I  started  a 
series  of  observations  on  the  growth  of  animals, 
which  have  been  continued  for  a  long  period,  during 
which  the  research  has  expanded  far  beyond  its 
original  scope.  While  carrying  forward  my  experi- 
ments on  orrowth,  various  conclusions  sueafested  them- 
selves  ;  some  tentative,  others  more  or  less  definite. 
These  have  been  partially  and  briefly  published  at 
various  times.^  To  review  these  publications  now 
would  serve  little  purpose  beyond  possibly  establish- 
ing the  claim  of  priority,  and  I  will  therefore  merely 
enumerate  them.  Moreover,  in  the  course  of  the 
following  pages  the  more  important  results  contained 
in  these  earlier  papers  are  brought  together.  My 
experiments  on  growth  led  to  a  memoir  ^  published 
in  1891,  in  the  English  Journal  of  Physiology.  It 
dealt  with  the  growth  of  guinea-pigs  and  is  to  be 
regarded  as  the  starting  point  or  foundation  of  the 
present  work.  Since  then  the  experimental  work 
has  been  continued,  and  data  concerning  the  growth 
of  other  animals  collected.  They  are  given  in  the 
course  of  the  following  pages. 

'  "Death  and  Individuality,"  y^iwrw.  Sci.,  vii.,  Ti-TJ  (1S85),  reprinted, 
Science,  iv.,  72-77. 

"  Researches  on  Growth  and  Death,"  Proc.  Soc.  Arts  (Mass.  Institute  Tech- 
nol.),     Meeting  310,  p.  50-56. 

"  The  Formative  Force  of  Organisms,"  Science,  vi.,  4-6  (18S5). 

"  Researches  on  Growth  and  Death  and  Biological  Problems,"  Proc.  Amer, 
Assoc.    Adv.  Sci.  for  1S84,  517-521. 

"The  Physical  Basis  of  Heredity,"  Science,  viii.,     125-130  (1886). 

^"Senescence  and  Rejuvenation,"  first  paper,  "On  the  Weight  of  Guinea- 
Pigs,"  Journ.  of  Physiol.^  xii.,  97-153,  pis.     I. -III.  (1891). 


INTRODUCTORY  LETTER  TO  SENATOR  M0S50  xv 

In  1890,  in  an  address^  delivered  before  the  Section 
of  Biology  of  the  American  Association  for  the 
Advancement  of  Science,  at  the  Indianapolis  meet- 
ing, I  first  presented  the  view  that  there  is  a  distinct 
correlation  between  the  amount  of  protoplasm  and 
the  rate  of  growth,  as  determined  by  the  experiments 
just  referred  to.  In  an  article ~  entitled  "Ueber  die 
Vererbung  und  die  Verjiingung,"  which  has  been 
translated  and  republished  in  the  Ame7'-ican  Natiir- 
alist,  certain  other  general  aspects  of  the  quantitative 
study  of  protoplasm  are  dealt  with.  Finally,  part  of 
the  conclusions  developed  were  embodied  in  the 
"Middleton  Goldsmith  Lecture,"^  before  the  New 
York  Pathological  Society,  in  March,  1901. 

May  I  explain  my  point  of  view  a  little  more  fully  ? 
The  proper  object,  the  final  purpose,  of  biology  is 
the  discovery  of  the  nature  of  life.  The  existence,  or 
non-existence,  of  a  vital  force  is  a  problem  concerning 
which  a  great  many  dogmatic  assertions  have  been 
put  forth.  It  is  evident,  however,  that  all  opinions 
as  to  the  essential  nature  of  vitality,  however  much 
they  have  differed  otherwise,  are  pretty  much  alike 
in  lackingf  both  scientific  foundation  and  intellectual 
value.     The    agnostic   position  is  the  only  possible 

1  "  On  Certain  Phenomena  of  Growing  Old,"  Proc.  Anier.  Assoc.  Adv. 
Science,  xxix. 

"^  "  Ueber  die  Vererbung  und  Verjungung,"  Biol.  Centralbl.,  xv.,  571-587. 
Transl."  "  On  Heredity  and  Rejuvenation,"  American  A^aturalist,  xxx,  i-g  ; 
S9-101. 

2  "The  Embryological  Basis  of  Pathology,"  Science,  N.  S.,  xiii.,  481-498  ; 
alsp  BQ?tgn  M(d.  Siir.  Journal,  cxliv.,  295-305. 


xvi  INTRODUCTORY  LETTER  TO  SENATOR  MOSSO 

and  defensible  one  for  a  scientific  man  to  occupy, 
who  is  loyal  to  the  spirit  of  research.  We  may  then 
assume  with  little  risk  of  mistake  that  no  hypothesis 
of  life  yet  offered  requires  serious  scientific  consider- 
ation. A  confession  of  agnosticism  is  here  a  positive 
contribution  to  the  truth.  On  the  other  hand,  there 
is  no  reason  for  giving  up  the  endeavour  to  get 
nearer  to  the  final  goal  of  biology  because  attempts 
to  reach  it  by  the  short  cut  of  speculation  have  always 
failed.  Indeed,  at  the  present  time  much  work  is 
being  done  towards  answering  general  questions,  the 
answers  to  which  appear  necessary  preliminaries  to 
attacking  the  problem  of  life  itself. 

Before  the  American  Association  for  the  Advance- 
ment of  Science,  in  1879,  I  read  a  paper  "  On  Condi- 
tions to  be  Filled  by  a  Theory  of  Life,"  which  was 
published  in  abstract  only.^  It  contained  an  enumera- 
tion, as  complete  and  exact  as  I  could  make  it,  of 
phenomena  which  any  tenable  hypothesis  of  vitality 
must  explain  ;  the  effort  being  made  to  generalise  the 
statements  to  the  farthest  legitimate  scientific  limit, 
thus  reducing  as  far  as  possible  the  number  of  phe- 
nomena. The  result  was  a  very  vivid  impression  on 
my  mind  of  the  inadequacy  of  all  hypotheses  of 
vitality,  and  that  impression  is  to-day  undisturbed. 
Had  circumstances  permitted  I  should  have  devoted 
myself  entirely  to  the  study  of  general  problems,  but 
necessity  early  led  me  into  teaching  embryology,  and 
in  the  acquisition  of  even  my  partial  mastery  of  that 

>  This  abstract  is  reprinted  as  Appendix  V  to  this  volume. 


INTRODUCTORY  LETTER  TO  SENATOR  M0550 xvii 

intricate  science  so  much  time  was  absorbed,  that  I 
was  forced  to  giv'e  up  the  hope  with  which  I  started 
out,  and  have  only  the  present  book  to  offer  as  a 
fragment  towards  the  fulfilment  of  the  original  plan 
of  researches  upon  general  biological  phenomena. 

If  one  starts  with  the  purpose  of  getting  nearer  a 
solution  of  the  final  problem  of  life,  it  is  not  difficult 
to  devise  numerous  researches  which  would  be  likely 
to  gain  for  us  insight  into  the  fundamental  phenomena 
of  biology.  It  was  from  the  indicated  standpoint 
that  it  seemed  to  me  that  one  of  the  most  promising 
opportunities  for  attack  was  offered  by  the  changes 
which  aofe  effects  in  oro-anisms.  These  chang^es  had 
been  then,  and  indeed  have  been  since,  very  little 
studied  in  a  systematic  way  or  from  any  general 
standpoint.  It  is  assuredly  one  of  the  most  general 
phenomena  in  the  life  history  of  organisms  that  they 
become  old.  From  the  ao^e  of  zero  at  the  moment 
of  sexual  impregnation,  animals  and  plants,  broadly 
speaking,  both  pass  through  a  series  of  changes  until, 
barring  accidents,  they  reach  their  limit  of  life  ;  by 
which  we  mean  the  maximum  longevity  achieved 
by  each  individual  under  the  optimum  of  conditions. 
Organisms  are  created  young  and  grow  old,  and  the 
old  produce  young  successors.  Senescence  is  a  pro- 
blem, of  living  matter,  and,  so  far  as  known,  has  no 
parallel  in  non-living  matter.  It  is  an  essential  feature 
of  life.  It  finds  its  most  familiar  expression  in  the 
gradual  loss  of  the  functional  powers  of  the  organ- 
ism, its  end  is  death.      My  book  is  the  outcome  of  an 


xviii   INTRODUCTORY  LETTER  TO  SENATOR  MOSSO 

attempt  to  learn  something  as  to  the  essential  character 
and  the  cause  of  that  loss. 

Age  causes  many  progressive  changes  in  the  or- 
ganism, but  none  which  are  more  obvious  and  more 
accessible  to  exact  study  than  those  of  growth.  Thus 
I  was  led  to  make  my  first  experiments  on  growth. 
It  soon  appeared  that  the  scope  of  the  inquiry  was 
expanding,  and  it  has  not  been  until  now  that  the 
matters  included  have  become  sufficiently  co-ordinated 
to  justify  their  collective  publication, — and  yet  the 
research  remains  fragmentary,  narrow,  and  incom- 
plete. I  can  make  no  pretence  of  having  solved  the 
manifold  problems  of  senescence,  but  I  hope  that  you 
will  at  least  find  some  of  them  more  clearly  formulated 
than  hitherto,  and  also  some  real  additions  to  our 
positive  knowledge. 

For  the  purpose  of  studying  growth  as  a  function 
of  age  it  was  desirable  to  eliminate  the  influence  of 
external  conditions  of  a  variable  character  as  far  as 
possible  ;  the  readiest  way  to  accomplish  this  was  to 
choose  a  self-regulative  organism ;  accordingly  one  of 
the  higher  vertebrates  was  considered  preferable,  be- 
cause of  all  organisms  they  are  the  most  independent 
of  outside  circumstances.  It  remained  only  to  pick 
out  a  convenient  species ;  various  considerations  led 
to  the  choice  of  the  guinea-pigs,  Cavi'a  cobaya.  This 
animal  offers  the  following  advantages  :  it  bears  con- 
finement well,  is  robust  and  but  little  liable  to  disease, 
breeds  readily,  is  easily  managed  and  fed,  and  gentle 
when  handled ;   its  maintenance  is  much  less  costly 


INTRODUCTORY  LETTER  TO  SENATOR  AdOSSOxix 

than  that  of  a  larger  animal,  an  important  considera- 
tion, as  upwards  of  one  hundred  were  kept  at  a  time 
for  several  years/  Another  important  advantage  de- 
pends on  the  fact  that  nearly  every  individual  is 
marked  with  spots  and  blotches  of  brown  and  black 
differently  from  all  others,  so  that  they  all  can  be 
readily  told  apart  without  any  artificial  marks,  and 
hence  it  is  easier  to  follow  the  growth  of  individuals. 
Occasionally  there  is  one  all  white,  but  such  white 
ones  can  be  marked  with  spots  of  nitrate  of  silver  on 
the  hair.  Guinea-pigs  are  so  unintelligent  that  I 
have  been  unable  to  feel  any  interest  except  scientific 
in  them,  which  perhaps  also  has  been  advantageous. 

Later,  as  recorded  in  Chapter  III.,  a  limited 
number  of  determinations  of  the  weight  of  growing 
rabbits  and  chickens  was  also  made. 

All  these  animals  were  kept  in  summer  in  suitable 
spacious  pens  in  the  country ;  in  winter,  in  large 
boxes  in  well  lighted  and  ventilated  rooms,  warmed 
by  artificial  heat.  They  were  carefully  tended  most 
of  the  time  by  myself ;  the  endeavour  was  to  secure 
continuously  the  best  hygienic  conditions  by  unremit- 
ting attention  ;  it  was  my  habit  to  make  two  visits 
daily.      They  were  fed  with  the  best  food  obtainable. 

To  measure  the  growth  the  weights  were  taken  of 
the  growing  and  adult  individuals,  the  weight  being 
the  only  available  measure  for  the  whole  animal,— 
and  the   only  one   permitting   comparisons   between 

'  During  one  winter  upwards  of  eighteen  barrels  of  carrots,  three  tons  of  hay, 
twenty-six  bushels  of  oats,  and  some  other  food  were  eaten  by  my  guinea-pigs. 


XX   INTRODUCTORY  LETTER  TO  SENATOR  MOSSO 

different  species  of  organisms.  The  weighings  were 
made  in  the  morning  before  the  animals  were  fed. 
But  they  were  kept  always  supplied  with  dry  oats  ; 
this  practice  is  desirable  because  it  helps  essentially 
in  preserving  the  animals  in  good  condition.  It  does 
not  entail  a  sufficient  error  in  the  weights  to  be  ob- 
jectionable,  because  it  is  more  or  less  constant  and  is 
not  very  large,  as  the  animals  will  not  eat  a  great 
deal  of  grain  when  they  have  plenty  of  other  food. 
No  fresh  food  was  left  in  the  pens  or  boxes  over 
nieht. 

In  all  the  weighings  there  is  necessarily  an  error. 
A  positive  error,  because  the  digestive  tract,  particu- 
larly the  wide  ccecum,  contains  always  considerable 
quantities  of  undigested  matter  ;  moreover,  the  blad- 
der may  hold  a  greater  or  less  quantity  of  urine. 
A  negative  error,  because  every  illness,  even  a  very 
slight  indisposition,  and  every  injury,  such  as  a  bite, 
for  instance,  causes  a  greater  or  less  loss  of  weight. 
The  quantitative  values  of  these  errors  are  presum- 
ably not  very  great ;  they  probably  counterbalance 
one  another  to  a  certain  extent  in  the  averages,  which 
may  be  accepted  as  approximately  accurate. 

The  advantage  of  these  experiments  over  statistics 
taken  from  man  lies  especially  in  the  fact  that  the 
same  individuals  are  followed  through  the  whole 
period  of  growth.  Otherwise  we  may  reach  errone- 
ous conclusions ;  thus  in  girls  there  is  a  very  great 
acceleration  of  growth  during  the  two  or  three  years 
preceding  puberty,  that  is,  the  epoch  of  the  first  men- 


INTRODUCTORY  LETTER   TO  SENATOR  MOSSO  xx\ 

struation  ;  the  acceleration  shows  itself  also  in  a  curve 
constructed  from  averages  taken  from  a  large  number 
of  observations  upon  many  girls,  but  the  variation 
appears  less  than  it  is  for  the  individual  and  gives 
therefore  an  erroneous  impression  of  the  actual  de- 
gree of  prepubertal  acceleration.  This  falsification 
necessarily  ensues  from  the  individual  variations  in 
the  age  of  the  first  menstruation, — for  the  accelera- 
tions in  one  girl  may  occur  at  an  older  age  than  in 
another  and  a  younger  age  than  in  a  third,  hence  when 
a  long  series  of  observations  is  averaged  the  result 
shows  an  acceleration  much  longer  in  duration,  but 
smaller  in  amount,  than  is  characteristic  for  the  in- 
dividual. Thus  Dr.  B.  A.  Gould  found  that  the 
stature  of  American  soldiers  increased  steadily  up  to 
thirty-five  years  to  1.7391  metres,  which  was  the 
maximum  average  height  for  any  age.  This  observa- 
tion does  not  prove  that  the  growth  period  for 
Americans  extends  to  thirty-five  years,  for  the  result 
noted  may  be  due  to  more  vigorous  men  growing 
more  and  surviving  (but  not  growing)  more  years 
than  the  smaller  and  weaker  men.  The  averag-e  at 
thirty-five  is  greater  than  at  thirty  because — if  the 
suggested  explanation  is  correct — the  shorter  men 
have  died  off.  This  might  be  decided  by  statistical 
study  of  the  relation  of  the  ages  at  death  from  dis- 
ease to  stature.  It  would  certainly  be  worth  while 
to  investigate  the  problem,  with  a  view  of  ascertain- 
ing whether  there  is  any  correspondence  between  the 
length  of  life  and  the  size  of  individuals.      A  positive 


^x\\  INTRODUCTORY  LETTER  TO  SENATOR  MOSSO 

answer  to  the  Inquiry  is  to  be  expected.  To  return  : 
— we  have  seen  that  if  we  do  not  compare  the  same 
individuals  with  one  another  we  cannot  be  sure  of 
correctly  measuring  the  phases  of  growth.  As  guinea- 
pigs  nearly  complete  their  growth  in  one  year,  it  was 
possible  to  make  the  requisite  number  of  observations 
within  a  reasonable  period,  which  Is  not  the  case  with 
man. 

In  regard  to  my  studies  on  the  structure  of  cells  in 
relation  to  growth,  nothing  special  as  to  methods  is 
to  be  said,  as  I  have  employed  only  the  well-known 
standard  procedures  of  histologists  and  embryol- 
oglsts. 

If  the  conclusions  formulated  In  this  book  con- 
cerning cytomorphosis,  senescence,  and  rejuvenation 
are  correct,  they  will  have  direct  bearing  on  many 
lines  of  investigation  concerning  growth,  reproduc- 
tion, regeneration,  degeneration,  and  pathological 
changes.  If  the  conclusions  are  correct  they  will 
open,  I  hope,  the  way  to  many  new  interpretations. 
But  I  must  stop. 

Let  me,  however,  close  this  lengthy  letter  with  the 
request  that  you  accept  the  dedication  of  this  volume 
as   a  memento   of    our   long   friendship,   and    as    an 
expression  of  my  admiration  and  attachment. 
Yours  faithfully, 

Charles  Sedgwick  Minot. 

Harvard  Medical  School, 
Boston,  Massachusktts,  Jan.   13,   1908. 


The    Problem    of 
Age,  Growth,  and  Death 


PROBLEM  OF  AGE,  GROWTH 
AND  DEATH 


THE    CONDITION    OF    OLD    AGE 

THE  subject  of  age  has  ever  been  one  which  has 
attracted  human  thought.  It  leads  us  so  near 
to  the  great  mysteries  that  all  thinkers  have  contem- 
plated it,  and  many  are  the  writers  who  from  the 
literary  point  of  view  have  presented  us,  sometimes 
with  profound  thought,  often  with  beautiful  images 
connected  with  the  change  from  youth  to  old  age. 
We  need  but  to  think  of  two  books  familiar  more  or 
less  to  us  all — that  ancient  classic,  Cicero's  De  Senec- 
tute,  the  great  book  on  age,  one  might  almost  say, 
from  the  literary  standpoint,  and  that  of  our  own 
fellow-citizen,  my  former  teacher  and  professor  at  the 
Medical  School,  Dr.  Holmes,  who  in  his  delightful 
Autocrat  offers  to  us  some  of  his  charming  specula- 
tions upon  age.  From  the  time  of  Cicero  to  the  time 
of  Holmes  numerous  authors  have  written  on  old 
age,  yet  among  them  all  we  shall  scarcely  find  any 


2  AGE,  GROWTH,  AND  DEATH 

one  who  had  title  to  be  considered  as  a  scientific 
writer  upon  the  subject.  Longevity  is  indeed  a 
strange  and  difficult  problem.  Many  of  you  doubt- 
less have  had  your  attention  directed  recently  to  the 
republished  translation  of  Cornaro's  famous  work^ 
and  know  how  sensible  that  is,  and  as  you  read  it  you 
must  have  perceived  how  little  in  the  practical  aspect 
of  the  matter  we  have  passed  beyond  the  advice 
which  old  Cornaro  gave  to  us,  and  yet  silently  in  the 
medical  laboratories,  and  in  the  physiological  and 
anatomical  institutes  of  various  universities,  we  have 
been  gathering  more  accurate  information  as  to  what 
is  the  condition  of  persons  who  are  very  old.'^ 

We  know,  first  of  all,  from  our  common  observation, 
that  the  very  old  grow  shorter  in  stature.  We  see  that 
they  are  not  so  tall  as  in  the  prime  of  life.  The  fig- 
ures which  have  been  compiled  upon  this  subject  are 
instructive,  for  they  show  that  at  the  age  of  some 
thirty  years  the  average  height  of  men — these  figures 
refer  to  Germans — is  1 74  centimetres.  It  remains  at 
that,  however,  only  for  a  short  period ;  then  it  decreases 

'  Luigi  Cornaro's  work  was  originally  published  at  Padua  in  1558  under  the 
title  of  Traitato  de  la  vita  sobria,  English  editions  have  been  issued  by 
George  Herbert,  by  an  anonymous  editor  (London,  1768),  and  G.  H.  Evans 
(1836),  all  which  included  other  "discourses."  The  translation  alluded  to  in 
the  text  was  issued  at  Milwaukee  in  1903  by  Wm.  F.  Butler,  and  in  the  same 
volume  the  reader  will  find  more  apposite  matter,  Cornaro  was  born  in  1464 
and  died  in  1566.  "  He  resigned  his  last  breath  without  any  agony,  sitting  in 
an  elbow  chair,  being  above  an  hundred  years  old." 

^  Addison,  in  the  Spectator  (Oct.  13,  1711),  wrote  of  Cornaro  and  thus  com- 
mends him :  "  The  '  Treatise'  I  mention  has  been  taken  notice  of  by  several 
v-minent  authors,  and  is  written  with  such  a  spirit  of  cheerfulness,  religion,  and 
good  sense,  as  are  the  natural  concomitants  of  temperance  and  sobriety." 


Fig.  I.  Two  Human  Vertebral  Columns  in  Section.  A,  female  of 
about  35  years.  B,  male  of  83  years  (an  extreme  case  of  senile  fusion  and 
flexure  of  the  vertebrae). 

3 


4  AGE,  GROWTH,  AND   DEATH 

and  at  forty  it  is  already  less  ;  at  fifty  decidedly  less  ; 
and  at  sixty  the  change  has  become  more  marked  ;  un- 
til at  seventy  years  v/e  find  that  the  height  has  shrunk 
from  174  to  161.  There  it  remains,  or  thereabouts, 
through  the  remainder  of  life,  though  there  may  be 
a  small  further  diminution.  This  decrease  in  stature 
is  due  largely  to  the  changes  in  the  vertebral  column. 
First  of  all  there  is  a  stoop.  The  vertebral  column 
is,  to  be  sure,  never  straight,  but  in  old  age  it  be- 
comes more  curved,  and  the  result  is  a  falling  of  the 
total  stature.  But  this  is  not  the  chief  cause,  for  in 
addition  to  this  the  softer  cartilages  and  elements  of 
the  spinal  column  become  harder,  change  into  bone, 
and  as  that  change  occurs  they  acquire  a  less  extent 
and  become  smaller,  and  the  result  is  that  the  verte- 
bral column  as  a  whole  collapses  somewhat  and  thus 
increases  the  diminution  of  height. 

We  find,  as  we  look  at  the  old,  a  great  change  to 
have  come  over  the  face.  The  roundness  of  youth 
has  departed ;  the  cheeks  are  sunken  ;  the  eyes  have 
fallen  far  back ;  the  lips  are  drawn  in.  All  of  these 
changes  indicate  to  us,  when  we  think  upon  them, 
the  fact  that  there  has  been  a  certain  shrinkage  and 
shrivelling  of  that  which  is  within  and  beneath  the 
skin.  Expressed  in  technical  terms,  we  should  call 
this  an  atrophy,  and  to  anatomists  the  mere  sight  of 
the  face  of  a  very  old  person.  Fig.  2,  reveals  at  once 
this  fundamental  fact  of  an  atrophy  of  the  parts,  an 
actual  loss  of  some  of  their  bulk,  which  is  one  of 
the  most  characteristic  and  fundamental  marks  of  old 


THE  CONDITION   OF  OLD  AGE  5 

age.  The  gait  becomes  shuffling,  the  foot  is  no 
longer  Hfted  free  from  the  ground,  as  the  old  man 
walks  along.  He  does  not  rise  upon  his  toes,  but 
the  sole  of  the  foot  is  kept  nearly  fiat  and  as  he  drags 
it  cumbrously  forward  it  is  apt  to  strike  upon  the 
sidewalk.  This  indicates  to  the  physiologist  a  less- 
ened power  in  the  muscles,  a  lessened  control  over 
the  action  of  these  muscles,  an  inferior  co-ordination 
of  the  movements,  so  that  there  has  been  in  the  old 
man,  judged  by  his  gait  alone,  a  physiological  deteri- 
oration as  well  as  an  anatomical  atrophy.  We  notice 
too  his  slow  speech,  often  difficult  hearing,  and  im- 
perfect sight. 

All  of  these  qualities  show  a  loss,  and  we  commonly 
think  of  the  old  as  those  who  have  lost  most,  who 
have  passed  beyond  the  maximum  of  development 
and  are  now  upon  the  path  of  decline,  going  down 
ever  more  rapidly.  One  of  the  chief  objects  at  which 
I  shall  aim  in  this  course  of  lectures  will  be  to  explain 
to  you  that  that  notion  is  erroneous,  and  that  the 
period  of  old  age,  so  far  from  being  the  chief  period 
of  decline,  is  in  reality  essentially  the  period  in  which 
the  actual  decline  going  on  in  each  of  us  will  be  least. 
Old  age  is  the  period  of  slowest  decline — a  strange, 
paradoxical  statement,  but  one  which  I  hope  to  jus- 
tify fully  by  the  facts  I  shall  present  to  you  in  this 
course. 

In  the  old  person  you  note  that  there  is  in  the 
mind  some  failure  and  also  loss  of  memory — less 
mental    activity,   greater   difficulty   in  grasping  new 


Fk;.  2.  Photograph  of  Chevreul,  taken  on  his  one  hundredth  birthday. 
He  was  asked  to  write  in  an  album  and  replied :  "  Que  voulez  vous :  que  j'ecrive 
sur  votre  album  ?  Je  vais  ecrire  mon  premier  principe  philosophique,  ce  n'est 
par  moi,  quil'ai  formule,  c'est  Malebranche — 'On  doit  tendre  avec  effort  k 
I'infallibilite,  sans  y  pretendre.' "  Chevreul  was  born  Aug.  31,  1786,  and  died 
Aug.  9,  1889.  For  the  privilege  of  using  this  portrait  I  am  indebted  to  Dr. 
Henry  P.  Bowditch,  to  whom  the  interesting  original  belongs. 

6 


Fig.  3.  Photograph  from  a  Child  at  Birth.  The  photograph  is 
owned  by  Dr.  H.  P.  Bowditch,  by  whose  courtesy  the  present  reproduction  is 
published. 


(C)     Adult,  thirty  years,  very  much  reduced  from  life. 


Fig.  4.  Ribs  and  Siernum,  to  show  the  progressive  ossihcation  of  the  carti- 
lage, which  is  indicated  by  stippling. — From  specimens  in  the  Warren  Museum 
of  the  Harvard  Medical  School. 


lo  AGE,  GROWTH,  AND  DEATH 

thoughts,  assimilating  new  ideas,  and  in  adapting  him- 
self to  unaccustomed  situations.  All  this  betokens 
again  the  characteristic  loss  of  the  old.  And  as  we 
turn  now  from  these  outward  investigations  to  those 
which  the  anatomist  opens  up  to  us,  we  learn  that  in 
the  interior  of  the  body,  and  in  every  organ  thereof, 
the  species  of  change  which  I  have  referred  to  as 
characteristic  of  the  very  old  is  going  on  and  has  be- 
come in  each  part  well  marked.^  Let  us  first  examine 
the  skeleton.  In  youth  many  parts  of  the  skeleton 
are  soft  and  flexible,  like  the  gristles  and  cartilages 
which  join  the  ribs  to  the  breastbone,  but  in  the  old 
man  these  are  largely  replaced  by  bone.  Bone  repre- 
sents an  advance  in  organisation,  in  structure,  as  we 
say,  over  the  cartilage.  The  old  man  has  in  that 
respect  progressed  beyond  the  youthful  stage  ;  but 
that  progress  represents  not  a  favourable  change  ;  the 
alteration  in  structure  from  elastic  cartilage  to  rigid 
bone  is  physiologically  disadvantageous,  so  that 
though  the  man  has  progressed  in  the  organisation 
or  anatomy  of  his  body,  he  has  really  thereby  rather 
lost  than  gained  ground.  Indeed  in  the  skeleton  this 
principle  of  loss  is  already  revealing  itself.^  In  the 
interior  of  the  bones  of  the  arms,  of  the  legs,  we  find 

'  Especially  valuable  are  the  data  concerning  men  and  women  of  over  eighty 
years  collated  by  Sir  George  M.  Humphry,  in  his  book,  Old  Age,  published  at 
Cambridge  (England)  by  Macmillan  &  Bowles  in  1889. 

^  The  senile  alterations  in  the  jaw  of  man  have  been  studied  by  Josef  Kieffer, 
("  Beitrage  zur  Kenntniss  der  Veranderungen  am  Unterkiefer  und  Kiefergelenk 
des  Menschen  durch  Alter  und  Zahnverlust,"  Zeitschr,  fiir  Morphol.  u.  An- 
thropol.,  xi,  1-82,  Taf.  i-iv,  1907).  An  important  paper,  offering  good  illus- 
trations of  the  general  principles  described  in  the  course  of  the  present  lecture. 


Ill 


THE  CONDITION  OF  OLD  AGE  n 

a  spongy  structure,  bits  of  bone  bound  together  in 
many  different  directions,  as  are  the  spicules  or  fibres 
in  a  sponge,  and  by  being  bound  so  together  they 
unite  hghtness  with  strength.  As  you  know,  a  col- 
umn of  metal,  if  hollow,  is  stronger  than  the  same 
amount  of  metal  in  the  form  of  a  rod.  So  with  the 
bones.  If  they  have  this  spongy  structure,  if  their 
interiors  are  full  of  little  cavities  with  intervening 
spicules  acting  as  braces  in  every  direction,  then  they 
acquire  great  strength  with  little  material  (Fig.  5). 
Now  in  the  old  much  of  the  internal  spongy  structure 
is  dissolved  away  and  there  is  left  (Fig.  6)  barely 
more  than  an  external  shell.  Partly  on  this  condition 
depends  the  greater  liability  of  the  bones  in  the  old 
person  to  break.  If  we  examine  the  muscles  we  see 
that  they  have  become  less  in  volume,  and  when  we 
apply  the  microscope  to  them  we  see  that  the  single 
fibres  on  which  the  strength  of  the  muscles  depends 
have  become  smaller  in  size  and  fewer  in  number.^ 
Professor  B.  Morpurgo  ^  by  an  ingenious  experiment 
has  demonstrated  that  exercise  increases  the  size  of 
the  muscles  by  increasing  the  size  of  the  single  fibres. 
|,  Exercise  produces  a  true  physiological  hypertrophy 
''  but  no  increase  in  the  number  of  the  fibres.  This 
important  discovery  suggests  the  idea  that  senile 
muscular  diminution  is  due  chiefly  if  not  exclusively 

'  This  statement  is  the  one  currently  accepted — but  I  have  found,  as  yet,  no 
exact  investigation  upon  the  relative  size  and  number  of  the  muscle  fibres  in 
old  persons. 

^  B.  Morpurgo,  "  Ueber  Activitats-hypertrophie  der  wilkiirlichen  Muskeln," 
Virchows  Arch.  Pathol.,   Bd.  cl.,  522-554  (1897). 


Fig.  5.  Section  of  the  Head  of  the  Thigh  Bone  of  a  Man  of  Thirty- 
seven  Years. — Compare  Fig.  6. 


'*?!?  **:' 


'.^2*^ 

*'!^'^' 


Fig.  6.  Section  of  the  Head  of  the  Thigh  Bone  of  a  Woman  of 
Eighty-two  Years. — Compare  with  Fig.  5,  and  note  the  loss  of  the  spongy 
bone  in  the  older  femur. 


13 


14  AGE,  GROWTH,  AND  DEATH 

to  the  reduction  in  size  of  the  single  fibres.  The 
muscle  has  actually  lost ;  it  is  inferior,  physiologic- 
ally speaking,  to  what  it  was  before.  You  remem- 
ber how  melancholy  Jacques  reminded  us  of  this  fact 
in  speaking  of  the  hose  "a  world  too  wide  for  his 
shrunk  shank."  His  saying  is  justified  by  the  loss  of 
the  muscles  in  volume  and  strength.  The  same  phe- 
nomenon of  atrophy  shows  itself  in  the  digestive 
organs.  Those  minute  structures  in  the  wall  of  the 
stomach  by  which  the  digestive  juice  is  produced 
undergo  a  partial  atrophy,  in  consequence  of  which 
they  are  less  able  to  act ;  they  are  not  so  well  organ- 
ised, therefore  not  so  efficient  as  in  earlier  stages. 
The  lungfs  become  stiffened ;  the  walls  which  divide 
off  an  air  cavity  from  the  neighbouring  air  cavities 
do  not  remain  so  thin  as  in  youth,  but  become  thick- 
ened and  hardened,  and  the  vital  capacity  of  the 
lungs,  that  is  to  say  the  capacity  of  the  lungs  to  take 
in  and  hold  air,  is  by  so  much  lessened.  The  heart — 
[it  seems  curious  at  first — is  in  the  old  always  en- 
larged; but  this  does  not  represent  a  gain  in  real 
power.  On  the  contrary,  if  we  study  carefully  the 
condition  of  the  circulation  of  the  blood  in  the  old, 
we  find  that  the  walls  of  the  large  blood-vessels 
which  carry  the  blood  from  the  heart  and  distribute 
it  over  all  parts  of  the  body — vessels  which  we  call 
arteries — have  lost  the  elastic  quality  which  is  proper 
to  them  and  by  which  they  respond  favourably  to  the 
pumping  action  of  the  heart.  Instead  they  have  be- 
come hard  and  stiff.     We  call  this  by  a  Greek  term 


THE  COXDITIOX  OF  OLD  AGE  15 

for  hardeninof,  sclerosis,  and  arterial  sclerosis  is  one 
of  the  most  marked  and  striking  characteristics  of 
old  persons.  Now  when  the  arteries  become  thus 
stiffened,  it  requires  a  greater  force  and  greater  effort 
of  the  heart  to  drive  the  blood  through  them,  and  in 
response  to  this  new  necessity,  the  heart  becomes 
enlarged  in  an  effort  of  the  organism  to  adapt  itself 
to  the  new  unfavourable  condition  of  the  circulation 
established  by  age.  But  the  power  of  the  heart  be- 
comes inferior  along  with  the  hypertrophy  or  enlarge- 
ment of  the  organ  and  we  see  that  in  the  old,  in 
order  to  make  up  for  the  feebleness  of  the  enlarged 
heart,  it  beats  more  frequently.  In  other  words,  the 
pulse  rate  in  the  old  person  increases.^  We  lind,  for 
instance,  that  at  the  time  of  birth  the  pulse  is  at  the 
rate  of  134  beats  to  a  minute.    It  rises  slightly  during 

'  My  friend.  Professor  W.  T.  Porter,  has  had  the  kindness  to  compile  the 
accompanying  table  for  me.  showing  the  pulse  frequency  from  one  to  eighty 
years.  For  the  first  two  months  after  birth  the  rate  is  about  130,  after  the 
third  month,  140.     The  fcEtal  rate  is  135  to  140. 


.  Mean  .  Mean  .  !Mean 

°  Frequency  °  Frequency  °  Frequency 

0-  1 134  13-14 87  25-30  72 

1-  2 Ill  14-15   -    ...  82  30-35  70 

2-3 108  15-16 83  35-40  72 

3-4 loS  16-17 So  40-45  72 

4-5 103  17-18     76  45-50  72 

5-6 gS  18-19 77  5C^55  72 

6-  7 93  19-20 74  55-60 75 

7-  8 94  20-21 71  60-65  73 

8-9 89  21-22 71  65-70 75 

9-10 91  22-23  70  70-75  75 

TO-II 87  23-24 71  75-SO  72 

I  [-12 89  24-25 72  80  and  over 79 

12-13 88 


1 6  AGE,  GROWTH,  AND  DEATH 

the  first  three  months  of  infancy  until  at  the  end  of 
the  third  month  it  reaches  some  140  beats  a  minute; 
it  soon  falls  off,  however,  and  at  the  end  of  the  first 
year  it  has  sunk  to  1 1 1  ;  at  five  or  six  years  it  be- 
comes 98,  and  at  twenty-one  years  it  has  sunk  to  71 
or  72.  There  are  thereafter  certain  minor  fluctua- 
tions in  the  rate  of  the  heart-beat  with  advancing 
age,  but  generally  it  may  be  said  that  this  value  of 
72  beats  a  minute  is  characteristic  of  adult  life.  But 
when  a  person  becomes  eighty  years  old,  it  has  been 
found  that  upon  the  average  the  rate  of  the  heart- 
beat rises  and  becomes  79  a  minute.  Hence  it  is 
clear  that  though  the  heart  is  larger,  it  has  to  make  a 
greater  effort,  that  is  to  say  a  more  frequent  beat,  in 
order  to  maintain  the  necessary  circulation  of  the 
blood. 

Another  illustration.  We  can  demonstrate  by 
going  back  to  the  anatomical  examination  of  the 
body,  that  those  important  structures  which  we  call 
the  germ  cells,  upon  which  the  propagation  of  the 
race  depends,  and  which  present  under  the  microscope 
certain  clearly  recognised  characteristics  by  which 
they  can  be  distinguished  from  all  other  cells  of  the 
body, — that  these  germ  cells  cease  their  activity  alto- 
gether in  the  very  old,  and  one  of  the  great  functions 
of  life  is  thus  blotted  out  altogether  from  the  history 
of  the  individual. 

Turning  now  to  the  yet  nobler  organs,  especially 
the  brain,  we  see  a  curious  change  going  on,  a  change 
of  which  old  age  presents  to  us  the  culminating  re- 


THE  CONDITION  OF  OLD  AGE  17 

cord.  In  order  to  study  the  weight  of  the  brain,  it  is 
necessary  to  compare  people  of  the  same  size,  for  the 
size  and  weight  of  the  brain  depend  somewhat  upon 
the  size  of  the  individual.  Now  it  has  been  discov- 
ered by  careful  examination  of  persons  of  similar  size 
that  the  brain  begins  relatively  early  to  diminish  its 
weight.  Thus  in  persons  of  a  height  of  175  centi- 
metres, and  over,  of  the  male  sex,  it  is  found  that  in 
the  period  from  twenty  to  forty  years  the  brain 
weight  is  1409  grams.  But  from  forty-one  to  seventy 
years  it  has  sunk  to  1363,  and  in  persons  of  from 
seventy-one  to  ninety  it  has  shrunk  to  1330.  Women 
of  equal  size  are  not  usual,  and  a  more  average 
height  for  women  is  165  centimetres;  a  woman  of 
such  a  height  is  likely  to  have — among  the  white 
races,  be  it  understood — at  twenty  to  forty  years  a 
brain  of  1265  grams,  at  forty  to  seventy  years  of  1200 
and  at  seventy-one  to  ninety  years  of  only  1 166  grams.^ 
I  give  these  figures  because  they  show  that  there 
is  no  guessing,  but  a  definite,  positive  knowledge, 
proving  that  soon  after  the  maturity  of  life  in  the 
individual    is    reached,    the    shrinkage    of    the    brain 

'  Ernst  Handmann  has  recently  published  statistics  on  the  growth  of  brain, 
based  on  measurements  at  the  Leipzig  Pathological  Institute.  See  Archiv  f, 
Anat.  u.  Entwickelungsges.,  1906,  p.  i.  The  following  summarises  his 
results : 

Brain  Weight  in  Grams 
Age  Male  Female 

4-  6 1215  iig4 

7-14 1376  1229 

15-49 1372  1249 

50-84(89) 1332  1196 


1 8  AGE,  GROWTH,  AND  DEATH 

begins,    and   then    continues   almost   steadily  to  the 
very  end  of  life.^ 

It  is  not  only  the  anatomist,  but  it  is  perhaps  almost 
equally  the  physiologist  who  gives  us  insight  into  the 
changes  which  go  on  in  the  old.  I  spoke  a  few  mo- 
ments ago  of  the  pulse  rate,  and  of  the  change  which 
that  offers.  At  first  sight  it  seems  as  if  a  greater 
pulse  rate  indicated  an  improvement,  but  if  you  recall 
the  explanation  given,  you  must  acknowledge  that 
this  is  by  no  means  an  acceptable  interpretation,  but 
that  on  the  contrary  the  change  is  a  clear  mark  of 
enfeeblement.  In  the  respiration,  also,  we  observe  a 
like  change.  Here  the  comparison  is  not  quite  so 
easy  as  we  should  at  first  imagine,  because  there  is  a 
relation  between  the  size  of  the  individual  and  the 
respiration.  The  respiration,  as  you  all  know,  frees 
the  body  from  the  products  of  combustion,  particu- 
larly from  that  product  which  we  know  as  carbon 
dioxide.  The  result  of  the  combustion  going  on  in 
the  body  (which  in  one  of  its  end  terms  appears  to  us 
as  carbon  dioxide  expelled  from  the  lungs)  is  to  pro- 
duce heat,  to  develop  the  necessary  warmth  for  the 
maintenance  of  the  proper  temperature  of  the  body. 
Now  in  the  very  young  the  bulk  of  the  body  is  not 
great,  but  the  loss  of  heat  is  very  great,  and  this  per- 
haps can  be  most  readily  explained  to  you  if  you 
imagine   that  you    hold  in   one    hand   a  very  small 

•  For  further  details  the  reader  is  referred  to  the  invaluable  work  by 
Professor  H.  H.  Donaldson  of  the  Wistar  Institute,  The  Growth  of  the 
Brain.  A  Study  of  the  Nervous  Systej?t  in  delation  to  Education,  l2mo, 
London,  1895  (Walter  Scott). 


THE  CONDITION  OF  OLD  AGE  19 

potato  and  In  the  other  a  very  large  potato,  both  of 
which  have  come  at  the  same  moment  from  the  same 
oven,  and  that  you  have  just  started  out  for  a  cold 
winter  drive.  You  all  know,  of  course,  that  in  a  little 
while  the  small  potato,  though  it  was  as  hot  as  the 
large  one  at  first,  will  have  lost  its  heat,  will  no  longer 
serve  to  keep  the  hand  warm,  but  the  other  hand,  in 
which  the  bulkier  potato  is  held,  in  which  the  volume 
of  the  heat — we  might  so  express  it,  perhaps — is  cor- 
respondingly great,  benefits  by  the  retained  heat  a 
long  time.  Essentially  similar  to  this  is  the  difference 
between  the  child  and  the  adult.  The  child  loses 
heat  with  comparatively  great  rapidity — the  old  per- 
son at  a  comparatively  slow  rate.  Hence  it  is  neces- 
sary for  the  child  to  produce  more  warmth  in  order  to 
keep  up  the  natural  normal  temperature  of  the  body. 
When,  therefore,  we  find  that  in  the  old  person  the 
respiration  is  diminished,  and  that  the  production  of 
carbon  dioxide  from  the  lungs  is  greatly  lessened,  we 
are  not.  immediately  to  jump  at  the  conclusion  that 
the  quality  of  physiological  action  has  been  debased — 
that  we  see  here  a  sign  of  decrepitude.  On  the  con- 
trary, the  change  is  the  result  of  physiological  adapta- 
tion, of  suiting  the  performance  of  the  body  to  its 
needs.  This  is  one  of  the  great  wonders,  one  of  the 
mysteries  of  life,  of  which  we  here  have  a  sample, 
the  constant  adaptation  of  the  means  to  the  end. 
That  which  the  body  needs  is  done  by  the  body.  A 
child  needs  more  warmth,  and  its  body  produces 
more ;   the   old   person    needs   less   warmth,    and   his 


20  AGE,  GROWTH,  AND  DEATH 

body  produces  less.  How  this  is  accomplished  we 
are  unable  to  say,  but  constantly  we  see  evidence  of 
this  purposeful  accommodation  on  the  part  of  the 
body — what  is  called  by  the  physiologists  the  teleo- 
logical  principle,  the  adaptation  of  the  reaction  of 
the  body  to  its  needs.  There  are  innumerable  illus- 
trations of  this,  many  of  which  are  of  course  perfectly 
familiar  to  us,  although  perhaps  we  do  not  think  of 
them  as  illustrations  of  this  great  law  of  nature  ;  as, 
for  instance,  when  we  eat  a  meal,  and  the  presence  of 
food  in  the  stomach  calls  into  action  the  glands  in  the 
wall  of  the  stomach  by  which  the  digestive  juice  is 
secreted.  The  juice  is  produced  exactly  at  the  time 
when  it  is  needed.  Innumerable,  indeed,  are  the 
illustrations  of  this  fundamental  principle. 

There  is  another  class  of  phenomena  characteristic 
of  the  very  old  which  will  perhaps  seem  a  little  sur- 
prising to  you  after  the  general  tenor  of  my  previous 
remarks.  I  refer  to  the  power  of  repair.  This, 
modern  surgery  especially  has  enabled  us  to  recog- 
nise as  being  far  greater  in  the  old  than  we  were 
wont  to  assume  ;  and  we  know  that  there  is  a  certain 
luxury,  a  certain  excess  reserve  in  the  power  of  re- 
pair, and  that  we  may  go  far  beyond  the  ordinary 
necessities  of  our  life  in  our  demands  upon  our  or- 
ganism, and  still  find  that  our  body  is  capable  of 
making    the    necessary    response.^      Ordinarily    the 

'  A  most  valuable  and  suggestive  study  of  the  excess  supply  of  physiological 
resources  has  been  made  by  Dr.  S.  J.  Meltzer,  "  The  Factors  of  Safety  in  Animal 
Structure  and  Animal  Economy,"  Jotirnal  Avier.  Med.  Assoc,  vol.  xlviii, 
pp.  655-664. 


THE  CONDITION  OF  OLD  AGE  21 

amount  of  blood  which  we  require  is  moderate  in 
amount — moderate  in  the  sense  that  the  destruction 
of  the  blood  continually  going-  on  in  the  body  is  not 
a  very  rapid  process  ;  but  if,  through  some  accident, 
a  person  loses  a  large  quantity  of  blood,  then,  by  one 
of  these  teleological  reactions  of  which  I  have  spoken, 
the  production  of  new  blood  is  increased,  the  loss  is 
soon  made  up,  and  we  discover  that  the  blood,  so  to 
speak,  has  been  repaired.  Or  when  a  little  of  the 
skin  is  lost,  it  quickly  heals  over.  That  again  is  due 
to  the  power  of  repair.  Ordinarily  so  long  as  the 
skin  remains  whole  that  power  is  not  called  into  ac- 
tion, but  if  a  wound  comes,  then  the  regenerative 
force  resident  always  in  the  skin,  but  inactive,  comes 
into  play  and  produces  the  mending  which  is  such  a 
comfort.  So  in  old  people,  some  of  this  luxury  of 
reparative  power  persists,  so  that  they  can  recover 
from  wounds  in  a  far  better  way  than  we  should 
imagine  if  we  judged  them  only  by  the  general  phys- 
iological and  anatomical  decline  exhibited  through- 
out all  parts  of  the  body.  Some  of  the  luxury  of 
repair  comes  in  usefully  in  old  age. 

Now  if  we  consider  all  these  changes  in  the  most 
general  manner,  we  perceive  that  they  are  clearly  of 
one  general  character ;  they  imply  an  alteration  in 
the  anatomical  condition  of  the  parts ;  but  it  is  an 
alteration  which  does  not  differ  fundamentally  in  kind 
from  the  alterations  which  have  gone  on  before,  but 
it  does  differ  in  the  extent  and  in  part  in  the  degree 
to  which  these  alterations  have  taken  place.     When 


2  2  AGE,  GROWTH,  AND  DEATH 

the  elastic  cartilaginous  rib  becomes  bony,  nothing 
different  is  happening  from  that  which  happened  be- 
fore, for  there  was  a  stage  of  development  when  the 
entire  rib  consisted  of  cartilage,  and  in  the  progress 
of  development  toward  the  adult  condition  that  carti- 
lage was  changed  gradually  into  bone,  thus  producing 
the  characteristic,  normal,  efficient  bony  rib  of  the 
adult.  When  old  age  intervenes,  the  change  of  the 
cartilage  into  bone  goes  yet  further,  but  it  progresses 
in  such  a  way  that  it  is  no  longer  favourable,  but 
unfavourable.  We  have  then  in  this  case  a  clear 
illustration  of  a  principle  of  change  in  the  very  old 
which  is,  I  take  it,  perhaps  sufficiently  well  expressed 
by  saying  that  the  change  which  is  natural  in  the 
younger  stage  is  in  the  old  carried  to  excess.  But 
there  is,  in  addition  to  this,  something  more,  of  which 
I  have  already  spoken,  namely  the  atrophy  of  parts, 
'  and  by  atrophy  we  mean  the  diminution,  the  lessening 
of  the  volume  of  the  part.  There  is  a  partial  atrophy  of 
the  brain  in  consequence  of  which  that  organ  becomes 
smaller ;  there  is  an  extensive  atrophy  of  the  muscles 
in  consequence  of  which  their  volume  is  diminished, 
and  their  efficiency  decreased.  Atrophy  is  pre-em- 
inently characteristic  of  the  very  old,  and  we  see 
in  very  old  persons  that  it  becomes  each  year  more 
and  more  pronounced.  Indeed,  it  has  been  said 
recently  by  Professor  Metchnikoff,  a  distinguished 
Russian  zoologist,  now  connected  with  the  Pasteur 
Institute  in  Paris,  some  of  whose  publications  many 
of  you  have  doubtless  read,   that  his  conception  of 


THE  CONDITION  OF  OLD  AGE  23 

the  nature  of  senility,  of  old  age,  could  best  be  ex- 
pressed in  a  single  word,  atrophy.  "  On  resume  la 
senilite  par  un  seul  mot:  atrophie."^  That  is  his 
estimate  of  old  age.  But  that  is  not  the  only  es- 
timate of  old  age  which  has  been  made  up  to  the 
present  time.  We  find  one,  which  is  much  more 
prevalent,  is  that  which  connects  it  with  the  condition 
of  the  arteries.  Indeed,  Professor  Osier  has  written 
this  sentence  :  "  Longevity  is  a  vascular  question,  and 
has  been  well  expressed  in  the  axiom  that  a  man  is 
only  as  old  as  his  arteries."  ^  Now  these  are  medical 
views,  not  biological,  and  you  will  find  that  there  is  a 
very  extensive  literature  dealing  with  old  age  in  man 
based  upon  the  conception  that  old  age  is  a  kind  of 
disease,  a  chronic  disease,  an  incurable  disease.  Medi- 
cal writers  have  put  forward  various  conceptions  giv- 
ing a  medical  interpretation  of  this  disease.  That  to 
which  I  just  referred  is  the  favourite  one,  the  one 
you  are  most  likely  to  hear  from  physicians  to-day — 
namely,  the  theory  of  arterial  sclerosis,  that  the  hard- 
ening of  the  walls  of  the  arteries  is  the  primary  thing  ; 
it  interferes  with  the  circulation,  the  bad  circulation 
interferes  with  the  proper  working  of  every  part  of 
the  body,  and  as  the  circulation  becomes  impeded, 
various  accessory  results  are  produced  in  the  body  in 
consequence.  The  body  is  brought  to  a  lower  or 
more  diseased  condition  than  before.  Hence  many 
medical  writers  interpret  sclerosis  of  the  arteries  as 

*  L'Ann/e  biologique,  Tome  III.,  p.  256,  1897. 

'  W,  Osier,  The  Principles  and  Practice  of  Medicine,  i8g2,  p.  666. 


24  AGE,  GROWTH,  AND  DEATH 

the  primary  factor,  because  they  can  trace  so  many 
alterations  in  the  old  which  resemble  diseased  altera- 
tions to  the  natural  changes  in  the  arteries  by  which 
they  acquire  hardened  and  inelastic  walls,  which  pre- 
vent the  proper  response  of  the  artery  to  the  heart- 
beat, upon  which  the  normal  healthy  circulation 
largely  depends. 

Another  interpretation,  very  curious  and  interest- 
ing, is  that  which  has  been  recently  offered  by  the 
same  Professor  Metchnikoff  whom  I  have  just  men- 
tioned. He  has  written  a  book  upon  the  Nature 
of  Man,  translated  in  1903,  and  published  in  this 
country.  It  is  an  interesting  book.  It  gives  a  most 
attractive  picture,  incidentally,  of  Metchnikoff  him- 
self, a  man  of  pleasantly  optimistic  temperament,  but 
a  man  thoroughly  imbued  with  the  spirit  which  has 
so  often  been  attributed  to  contemporary  scientific 
men,  of  cold,  intellectual  regard  towards  everything, 
towards  life,  towards  man,  towards  mystery.  For 
him  mysteries  of  all  sorts  have  little  interest.  Those 
things  which  are  mysterious  are  beyond  the  sphere 
of  what  can  hold  his  attention.  He  must  reside  in 
the  clear  atmosphere  of  definite,  positive  fact.  This 
mental  bias  is  shown  in  his  book.  He  reviews  In  a 
happy  way  various  past  systems  of  philosophy ;  he 
describes  various  religions ;  and  he  points  out  his 
reasons  for  thinking  that  all  of  these  are  insufficient, 
that  there  is  no  satisfaction  to  be  derived  from  any 
of  the  ancient  philosophies  or  from  any  of  the  great 
world  religions.     Nevertheless  he  is  an  optimist.     He 


THE  CONDITION  OF  OLD  AGE  25 

has  noticed  as  a  result  of  his  meditations  upon  the 
arrangements  within  our  bodies  that  we  suffer  very 
much  from  what  he  calls  disharmonies,  by  which  he 
means  imperfect  adaptations  of  structures  within  us 
to  the  performance  of  the  body  as  a  whole.  He 
mentions  various  instances  of  such  disharmonious 
parts.  They  do  not  seem  to  me  quite  so  imposing 
as  apparently  they  do  to  him,  for  many  of  his  dis- 
harmonies are  based  upon  the  fact  that  we  do  not 
know  that  a  certain  structure  or  part  has  any  useful 
role  to  play  in  the  body.  But  I  am  inclined  to  sus- 
pect that  in  many  cases  it  is  only  because  we  are 
ienorant ;  the  list  of  useless  structures  in  the  human 
body  was  a  few  years  ago  very  long ;  it  has  within 
recent  years  been  greatly  shortened,  and  we  should 
learn  from  this  experience  a  caution  in  regard  to 
judging  about  these  things,  which,  I  think,  Professor 
Metchnikoff  has  failed  to  exert  duly  in  forming  his 
opinions  on  these  disharmonies.  Now  among  the 
disharmonies  which  he  recognises  is  that  of  the  great 
size  of  the  large  intestine,  which  is  of  such  a  calibre 
that  a  considerable  quantity  of  partially  digested  food 
can  be  retained  in  it  at  one  time.  When  such  food 
is  retained  in  the  intestine,  it  may  undergo  a  process 
of  fermentation.  There  are  many  sorts  of  fermenta- 
tion, and  some  of  them  produce  chemical  bodies  which 
are  injurious  to  the  human  organism.  Bacteria,  which 
will  cause  fermentation  of  this  sort,  do  actually  occur 
in  the  human  intestine.  Metchnikoff  thinks  that,  as 
we  grow  old,  this  tendency  to  fermentation  increases. 


2  6  AGE,  GROWTH,  AND  DEATH 

Now  the  bodies  produced  by  fermentation,  the  chem- 
ical bodies,  I  mean,  get  into  our  system  and  poison 
us.  The  result  of  the  poisoning  is  that  the  native 
capacities  of  the  various  tissues  and  organs  of  the 
body  are  lowered,  as  happens  in  a  man  "  intoxicated."  ^ 
All  parts  of  a  man  may  be  poisoned,  not  necessarily 
always  with  alcohol,  but  with  many  other  things  as 
well,  and  such  a  poisoning  Professor  Metchnikoff 
assumes  to  result  from  intestinal  fermentation.  More- 
over, he  has  further  observations,  which  lead  him  to 
the  idea  that  certain  cells  go  to  work  upon  the 
poisoned  parts  and  do  further  damage.  The  cells 
in  question  are  minute  microscopic  structures,  so 
small  that  we  cannot  at  all  see  them  with  the  naked 
eye,  but  which  have  a  habit  of  feeding  in  the  body 
upon  the  various  parts  thereof  whenever  they  get  a 
chance.  Cells  of  this  sort  go  by  the  scientific  name 
of  phagocytes,  which  is  merely  a  Greek  term  for 
"  eating  cells."  The  phagocytes,  for  instance,  devour  i 
pigment  in  the  hair,  and  in  old  persons  the  production ' 

•  The  "poison-theory"  of  old  age  and  death  has  recently  been  adopted  by 
Prof.  T.  H.  Montgomery,  Jr.,  who  has  written  :  "Perhaps  the  best  substan- 
tiated view  ...  is  that  natural  death  of  the  individual  results  from  self- 
poisoning.  The  waste  products  of  metabolism,  some  of  them  toxic,  accumulate 
in  the  tissues  until  there  results  a  true  intoxication  of  the  latter.  We  may  try 
to  transcribe  this  into  a  little  more  definite  physiological  phrase  :  death  follows 
on  account  of  the  insufficiency  of  the  excretion  process,  therefore  the  limit  of 
life  is  a  matter  of  excretion "  ( Transactions  Texas  Academy  of  Scietice,  ix, 
PP-  77.  78)'  The  author  gives  no  evidence  to  justify  these  assertions,  and  they 
are  therefore  hardly  available  for  discussion.  P.  yg,  Montgomery  dissents  from 
my  views  on  differentiation,  because  I  have  failed  to  recognise  "  the  underlying 
factor  of  senescence,  which  is  insufficiency  of  the  excretion  process."  The 
present  volume  aims  to  prove  that  the  underlying  factor  of  senescence  is  another 
than  that  assumed  by  Montgomery. 


THE   CONDITION  OF  OLD  AGE  27 

of  white  hair  has  resuhed  from  the  activity  of  phago- 
cytes which  have  eaten  the  pigment  which  should 
have  remained  in  the  hair  and  kept  its  colour.^  But 
the  pigment  of  the  hair  is  not  the  only  thing  they 
will  attack  ;  they  will  make  their  aggressive  inroads 
upon  any  part  of  the  body  ;  and  Professor  Metchnikoff 
has  advanced  the  theory  that  old  age  consists  chiefly 
in  the  damage  which  is  done  by  phagocytes  to  pois- 
oned parts  of  the  body,  the  poisoning  being  due  to 
the  fermentation  in  the  large  intestine.  Now  it  has 
been  observed  by  some  of  the  German  investigators  ^ 
of  these  matters  that  the  presence  of  lactic  acid  inter- 
feres with  this  fermentative  process  as  it  goes  on  in 
the  intestine.  Lactic  acid,  as  its  name  implies,  is  the 
characteristic  acid  which  occurs  in  milk  when  it  be- 
comes sour.  An  Italian  investio-ator'^  tried  drinking 
some  sour  milk  with  the  idea  of  stopping  the  fermenta- 
tion in  the  intestine,  and  so  putting  an  end  to  the  dele- 
terious change,  and  he  believes  in  the  short  time  that 
he  tried  it  that  it  did  him  good — quite,  you  see,  in 
the  way  of  a  patent  medicine.*  Professor  Metch- 
nikoff, on  this  basis,  has  recommended,  in  his  book 
on  the  Nature  of  Man,  the  regular  drinking  of  sour 

'  This  interesting  fact  was  discovered  by  Metchnikoff,  Annales  de  I'lnslilut 
Pasteur,  igoi,  p.  865. 

^  Compare  Bienstock,  Archiv  filr  Hygiene,  xxxix.,  p.  390  (1902)  ;  also 
Tissier  et  Martelly,  Annales  de  F Instittit  Pasteur,  1902,  p.  865. 

^  Albert  Rovighi,  '*  Die  Aetherschwefelsauren  im  Ham  und  die  Darminfec- 
tion,"  Zeitschr.  fiir  Physiol.  Chemie,  xvi.,  pp.  20-46  ;  see  especially  p.  43. 

*  Rovighi  used  "  kephyr,"  a  fermented  milk,  in  his  experiments.  For  the 
mode  of  preparation  and  for  the  use  of  "  kephyr,"  see  Fischer,  Die  netteren 
Arzneimitteln,  Berlin,  1887,  p.  169. 


28  AGE,  GROWTH,  AND  DEATH 

milk,^  in  the  hope  apparently  that  it  will  postpone 
senility,  and  will  leave  us  our  powers  in  maturity  long 
beyond  that  period  when  we  at  present  reach  the 
fulness  of  our  vigour,  and  advance  the  period  of  time 
when  the  changes  of  the  years  put  us  out  of  court. 
He  regards  this  as  an  optimistic  substitute  for  the 
various  forms  of  philosophy  and  religion  which  many 
millions  of  people  have  found  helpful  in  life,  and  cer- 
tainly it  is  the  cheapest  substitute  which  has  ever 
been  seriously  proposed. 

There  is  another  writer  who,  though  having  a  Ger- 
man name,  is  in  reality  a  Russian,  Professor  Miihlmann.^ 
He  has  another  theory  in  regard  to  the  fundamental 
nature  of  senility.  He  takes  such  instances  as  that 
which  I  spoke  of,  of  respiration  in  connection  with  the 
production  of  warmth  in  the  child's  body  and  in  the 
body  of  the  adult,  and  finds  that  the  diminution  of 
the  surface  in  proportion  to  the  bulk  of  the  body  is 
characteristic  of  the  old,  and  he  concludes  that  we  be 
come  old  because  we  do  not  have  proportionately  sur- 
face enough  left.      His  view  implies,  apparently,  that  if 

'  "  It  is  plain,  then,  that  the  slow  intoxications  that  weaken  the  resistance  of 
the  higher  elements  of  the  body  may  be  arrested  by  the  use  of  kephyr,  or  better 
still  of  soured  milk"  (Metchnikoff,  Nature  of  Man,  1903,  p.  255). 

"^  Miihlmann  has  published  several  papers  on  old  age,  which  contain  much 
valuable  and  original  matter.     The  following  may  be  specially  cited  : 

"  Weitere  Untersuchungen  iiber  die  Veranderung  der  nervenzellen  in  verschie- 
denem  Alter,"  Arch,  mikrosk.  Anat.,  Iviii.,  pp.  231-247  (1901). 

"  Ueber  die  Veranderungen  der  Hirngefasse  in  verschiedenem  Alter,"  Arch 
mikrosk.  Anat.,  lix.,  pp.  258-269  (igoi). 

His  general  views  are  presented  in  his  memoir,  Ueber  die  Ursache  des  Alters, 
Wiesbaden,  1900,  and  in  a  short  essay  in  the  Biologisches  Centralblatt,  Bd, 
XXI,  pp.  8x4-828. 


THE   CONDITION  OF  OLD  AGE  29 

we  could  keep  ourselves  more  or  less  of  the  stature 
of  pygmies  we  should  be  healthier  and  better  off.  I 
confess  these  theories,  and  many  others  which  I  might 
enumerate  to  you,  seem  to  me  to  be  somewhat  fan- 
tastic— odd  rather  than  valuable.  Yet  they  all  spring 
from  this  one  common  feeling,  which  is,  I  believe,  a 
sinister  influence  upon  the  thought  of  the  day  in 
regard  to  the  problem  of  age — they  spring  from  the 
medical  conception  that  age  is  a  kind  of  disease,  and 
that  the  problem  is  to  explain  the  condition  as  it 
exists  in  man.  Now  that  is  precisely  what  I  protest 
against.  What  I  hope  to  accomplish  in  these  lectures 
is  to  build  up  gradually  in  your  minds  some  acquaint- 
ance with  the  fundamental  and  essential  changes 
which  are  characteristic  of  age  and  in  regard  to  which 
we  have  been  learning  something  during  the  last  few 
years — I  might  almost  say  only  within  recent  years — 
and  by  means  of  this  exposition  to  give  you  a  broader 
view  and  a  juster  interpretation  of  the  problem.  I 
hope,  before  I  finish,  to  convince  you  that  we  are 
already  able  to  establish  certain  significant  generalisa- 
tions as  to  what  is  essential  in  the  change  from  youth 
to  old  age,  and  that  in  consequence  of  these  gen- 
eralisations, now  possible  to  us,  new  problems  present 
themselves  to  our  minds,  which  we  hope  really  to  be 
able  to  solve,  and  that  in  the  solving  of  them  we 
shall  gain  a  sort  of  knowledge,  which  is  likely  to  be 
not  only  highly  interesting  to  the  scientific  biologist, 
but  also  to  prove,  in  the  end,  of  great  practical  value. 
Surely  we   cannot   hope   to   obtain    any   power  over 


30  AGE,  GROWTH,  AND  DEATH 

age,  any  power  over  the  changes  which  the  years 
bring  to  each  of  us,  unless  we  understand  clearly, 
positively,  and  certainly,  what  these  changes  really 
are.  I  think  you  will  learn,  if  you  do  me  the  honour 
to  follow  the  lectures  further,  that  the  changes  are 
indeed  very  different  from  what  we  should  expect 
when  we  start  out  on  a  study  of  age,  and  that  the 
contributions  of  science  in  this  direction  are  novel 
and  to  some  degree  startling.  We  can  begin  to 
approach  this  broader  view  of  our  subject  if  we  pass 
beyond  the  consideration  of  man. 

If  we  turn  from  man  to  the  animals  which  we  are 
most  familiar  with,  the  common  domestic  quadrupeds, 
we  see  that  they  undergo  a  series  of  changes  not 
very  dissimilar  to  those  which  man  himself  must  pass 
through.  An  old  horse,  an  old  dog,  an  old  cat,  shows 
pretty  much  the  same  sort  of  decrepitudes  which 
characterise  old  men.  But  when  we  pass  farther 
down  in  the  scale  to  the  fishes,  or  even  to  a  frog,  we 
discover  great  differences.  Do  you  think  you  could 
tell  a  frog  when  it  is  old  by  the  way  it  walks — for  it 
never  walks — or  a  fish  by  the  amount  of  hardening 
of  the  lungs,  when  it  has  none  ?  Yet  the  lack  of 
lungs  is  characteristic  of  the  fish.  And  what  becomes 
of  the  theory  of  arterial  sclerosis  when  we  go  still 
lower  in  the  animal  kingdom,  towards  its  lowermost 
members,  and  find  creatures  which  live  and  thrive 
and  have  lived  and  thriven  for  countless  generations, 
yet  have  no  arteries  at  all  ?  They,  of  course,  do  not 
grow  old  by  any  change  of  their  arteries.      But  when 


THE  CONDITION  OF  OLD  AGE  31 

we  come  to  study  these  various  animals  more  care- 
fully, we  learn  that  in  them  the  anatomical  and  phy- 
siological features  which  I  have  indicated  to  you  in 
my  description  of  the  changes  in  the  human  being 
are  paralleled,  as  it  were,  by  similar  changes  ;  but 
only  by  similar,  not  by  identical,  changes.  If  we 
examine  the  insects,  for  instance,  we  see  that  in  an 
old  insect  there  is  a  hardening  of  the  outer  crust  of 
the  body  which  serves  as  a  shell  and  a  skeleton  at 
once.  That  hardening  increases  with  the  age  of  the 
individual.  We  can  see  in  the  insect  a  lessening 
development  of  the  digestive  tract,  and  we  can  see — 
it  has  been  demonstrated  with  particular  nicety — a 
degradation  of  the  brain.^  Insects  have  a  very  small 
brain,  but  when  a  bumblebee,  or  a  honeybee,  grows 
old,  as  he  does  in  a  few  weeks  after  he  acquires 
his  wings,  we  see  that  the  brain  actually  becomes 
smaller,  and  not  only  that,  but  as  I  shall  be  able 
to  demonstrate  to  you  with  the  lantern  in  the 
next  lecture,  the  elements  which  build  up  the  brain 
have  each  of  them  become  smaller  and  the  diminu- 
tion in  the  size  of  the  brain  is  due  in  part  to  the 
shrinkage  of  the  single  microscopic  constituents. 
There  is  another  point  of  resemblance.  We  find 
that  when  one  of  the  better  parts  of  the  body  under- 
goes an  atrophy,  it  becomes  not  only  smaller,  but  its 
place  is  to   a  certain  extent  taken  by  the   inferior 

'  C.  F.  Hodge,  "Changes  in  Ganglion-Cells  from  Birth  to  Senile  Death. 
Observations  on  Man  and  Honeybee,"  Journal  of  Physiology,  vol.  xvii.,  pp. 
129-134   (1894). 


32  AGE,  GROWTH,  AND  DEATH 

tissues — especially  by  those  which  we  call  comprehen- 
sively the  connective  tissues,  which  might  perhaps  be 
best  described  to  a  general  audience  as  that  which  is 
the  stuffing  of  the  body  and  fills  out  all  the  gaps 
between  the  organs  proper.  In  consequence  of  per- 
forming this  general  function,  they  are  very  properly 
called  connective  tissues,  since  they  connect  all  the 
different  organs  and  systems  of  organs  in  the  body 
together.  Now  in  every  body  there  is  a  continual 
fighting  of  the  parts.  They  battle  together,  they 
struggle,  each  one  to  get  ahead,  but  the  nobler 
organ,  generally  speaking,  holds  its  own.  There  are 
early  produced  from  the  brain  the  fine  bundles  of 
fibres  which  we  call  the  nerves,  which  run  to  the 
nose,  to  the  tongue,  and  to  the  various  parts  of  the 
body.  When  these  appear  all  the  parts  of  the  body 
are  very  soft.  Afterwards  comes  in  the  hard  and,  we 
should  think,  sturdy  bone,  but  never,  under  normal 
conditions,  does  the  bone  grow  where  the  nerve  is. 
The  nerve,  soft  and  pulpy  as  it  seems,  resists  abso- 
lutely the  encroachment  of  the  bone,  and  though  the 
bone  may  grow  elsewhere,  and  will  grow  elsewhere 
the  moment  it  gets  a  free  opportunity,  it  cannot 
beat  the  soft  delicate  nerve.^  Similarly  we  find  that 
the  substance  which  forms  the  liver  is  pulpy,  very 

'  The  nerve  fibres  of  the  olfactory  membrane  arise  very  early  in  the  embryo 
and  form  numerous  separate  bundles.  Later  the  bone  arises  between  the  bun- 
dles, for  each  of  which  a  hole  is  left  in  the  osseous  tissue,  so  that  the  bone  in 
the  adult  has  a  sieve-like  structure,  and  hence  is  termed  the  cribriform  plate. 
It  oiTers  a  striking  illustration  of  the  inability  of  hard  bone  to  disturb  soft 
nerve  fibres. 


THE  CONDITION  OF  OLD  AGE  ^^^ 

delicate.  Those  of  you  who  have  seen  fresh  liver  in 
the  butcher's  shop  know  what  a  flabby  organ  it  is,  and 
yet  though  it  is  surrounded  by  the  elements  of  con- 
nective tissue,  which  with  great  zest  and  eagerness 
produce  tough  fibres,  it  never  gives  way  to  them. 
The  connective  tissue  is  held  back  by  the  soft  liver 
and  kept  in  place  by  it.  The  liver  is,  so  to  speak,  a 
nobler  organ  than  the  connective  tissue  and  holds 
sway  ordinarily ;  but  in  old  age,  when  the  nobler 
organs  lose  something  of  their  power,  then  the  con- 
nective tissue  gets  its  chance,  grows  forward,  and  fills 
up  the  desired  place,  and  acquires  more  and  more 
a  dominating  position.  We  can  see  this  process  in 
the  brain  of  man  or  the  brain  of  the  bee.  That 
which  is  the  nervous  material  proper,  microscopic 
examination  shows  us  to  be  diminished  everywhere 
in  the  old  bee  and  in  the  old  man,  and  the  tissue 
which  supports  it,  which  is  of  a  coarser  nature  and 
cannot  perform  any  of  the  nobler  functions,  fills 
up  all  the  space  thus  left,  so  that  the  actual  composi- 
tion of  the  brain  is  by  this  means  changed.  There 
is,  you  see,  therefore,  during  the  atrophy  of  the  brain, 
not  only  a  diminution  of  the  organ  as  a  whole,  but 
there  is  the  further  degradation  which  consists  in  the 
yielding  of  the  nobler  to  the  baser  part,  if  I  may  so 
express  myself.  That,  you  recognise,  necessarily  im- 
plies a  loss  of  function.  The  brain  cannot  under 
senile  conditions  do  the  sort  of  fine  and  efficient  work 
which  it  could  do  before.  Now  if  we  go  on  from  in- 
sects to  yet  lower  organisms,  we  see  less  and  less 


34  AGE,  GROWTH,  AND  DEATH 

appearing  of  an  advance  in  organisation,  of  correlated 
loss  of  parts,  and  when  we  get  far  enough  down  the 
scale,  senescence  becomes  very  vague.  The  change 
from  youth  to  old  age  in  a  coral  or  in  a  sponge  is  at 
best  an  indefinite  matter. 

I  should  like,  did  the  length  of  the  course  permit, 
to  enlarge  greatly  upon  this  aspect  of  the  question, 
and  explain  to  you  how  it  is  that  as  the  organism 
rises  higher  and  higher  in  the  scale,  old  age  becomes 
more  and  more  marked,  and  in  no  animal  is  old  age 
perhaps  so  marked,  certainly  in  no  animal  is  it  more 
marked,  than  in  ourselves.  The  human  species 
stands  at  the  top  of  the  scale  and  it  also  suffers  most 
from  old  age.  We  shall  learn,  I  hope,  more  clearly 
later  on  in  the  course  of  these  lectures,  that  this  fact 
has  a  deeper  significance,  that  the  connection  be- 
tween old  age  and  advance  in  organisation,  advance 
in  anatomical  structure,  is  indeed  very  close,  and  that 
they  are  related  to  one  another  somewhat  in  fashion 
of  cause  and  effect ;  just  how  far  each  is  a  cause  and 
how  far  each  is  an  effect  it  would  perhaps  be  prema- 
ture to  state  very  positively  ;  but  I  shall  show  you,  I 
think  in  a  convincing  way,  that  the  development  of 
the  anatomical  quality,  or  in  other  words  of  what  we 
call  organic  structure,  is  ^Ae  fundamental  thing  in  the 
investigation  of  the  processes  of  life  in  relation  to 
age.  We  can  see  it  illustrated  again  very  clearly 
indeed  when  we  turn  to  the  study  of  plant  life,  for 
plants  also  grow  old.  Take  a  leaf  in  the  spring. 
It  is  soft  as  the  bud  opens.      The  young  leaf  is  deli- 


THE  CONDITION  OF  OLD  AGE  35 

cate.  It  has  a  considerable  power  of  growth.  It 
expands  freely,  and  soon  becomes  a  leaf  of  full  size. 
Then  comes  the  further  change  by  which  the  leaf 
gets  a  firmer  texture ;  the  production  of  anatomical 
quality  in  the  leaf,  so  to  speak,  goes  on  through  the 
summer,  and  the  result  of  that  advance  in  the  an- 
atomical quality  is  that  the  delicate,  youthful  softness 
and  activity  of  the  leaf  is  stopped.  It  cannot  grow 
any  more  ;  it  cannot  function  as  a  leaf  properly  any 
more.  The  development  of  its  structure  has  gone 
too  far  and  the  leaf  falls  and  is  lost,  and  must  be 
replaced  by  a  new  leaf  the  next  year.  When  we 
examine  the  changes  that  go  on  in  any  flowering 
plant,  we  observe  always  that  there  is  this  production 
of  structure,  and  then  the  decay,  the  end  or  death. 
At  first  structure  comes  as  a  helpful  thing,  increasing 
the  usefulness  of  the  part,  and  then  it  goes  on  too  far 
and  impairs  the  usefulness,  and  at  last  a  stage  is  pro- 
duced in  which  no  use  is  possible  any  longer — the 
thing  is- worthless.  It  is  cast  away  in  the  case  of  the 
plant  life ;  and  this  casting  away  of  the  useless  is  a 
thing  not  by  any  means  confined  to  plants ;  it  occurs 
equally  in  ourselves  all  the  time  ;  at  every  period  of 
our  life  we  have  been  getting  through  with  some 
portion  of  our  body;  that  portion  acquired  a  certain 
organisation,  it  worked  for  us  awhile,  and  then  being 
done  with  it,  we  threw  it  away  because  it  was  dead. 
Very  early  in  the  history  of  every  individual  there 
was  a  production  of  blood,  and  then  followed  the 
destruction  of  some  of  the  blood  corpuscles  and  their 


36  AGE,  GROWTH,  AND  DEATH 

remains  were  used  for  various  purposes.  The  pig- 
ment which  is  in  the  Hver  comes  from  the  destroyed 
blood  corpuscles,  and  it  is  believed  that  the  pigment 
which  colours  the  hair  is  derived  from  the  same 
source.  The  blood  corpuscles  contain  a  material 
which  when  chemically  elaborated  reappears  as  the 
deposit  which  imparts  to  the  hairs  their  colouration. 
You,  of  course,  are  all  familiar  with  the  loss  of  hair. 
It  occurs  to  everybody,  but  did  you  ever  think  that 
it  means  that  the  hair  which  has  lived  has  died,  and 
that  that  hair  which  was  a  part  of  you  has  been  cast 
off  ?  That  is  what  the  loss  of  hair  means  to  the  bi- 
ologist— the  death  of  a  part  and  the  throwing  away 
of  it,  and  it  is  typical  of  what  is  going  on  through 
the  body  all  the  time.  It  occurs  in  the  intestines, 
where  the  elements  which  serve  for  purposes  of 
digestion  are  continually  dying  and  being  cast  off. 
The  outer  skin  is  constantly  falling  off  and  being 
renewed,  and  that  which  goes  is  dead.  In  every  part 
of  the  body  we  can  find  something  which  is  dying. 
Death  is  an  accompaniment  of  development  ;  parts  of 
us  are  passing  off  from  the  limbo  of  the  living  all  the 
time,  and  the  maintenance  of  the  life  of  each  individ- 
ual of  us  depends  partially  upon  the  continual  death 
going  on  in  minute  fragments  of  our  body  here  and 
there. 

Our  next  step  in  this  course  of  lectures  will  carry 
us  into  the  microscopic  world,  and  with  the  aid  of 
the  lantern  at  the  next  lecture  I  shall  hope  to  demon- 
strate to  you  a  little  of  the  microscopic  structure  of 


THE  CONDITION  OF  OLD  AGE  37 

the  body  and  of  the  general  nature  of  the  change 
which  exhibits  itself  in  the  body  from  its  earliest  to 
its  latest  condition.  With  such  knowledge  in  our 
minds,  we  shall  be  able  next  to  study  some  of  the 
laws  of  growth.  We  shall  gain  from  our  microscopic 
information  a  deeper  insight  into  some  of  the  se- 
crets of  the  changes  which  age  produces  in  the 
human  body. 


II 

CYTOMORPHOSIS  I    THE    CELLULAR    CHANGES    OF    AGE 

TADIESAND  GENTLEMEN:  I  endeavoured 
in  my  last  lecture  to  picture  to  you,  so  far  as 
words  could  suffice  to  make  a  picture,  something  of 
the  anatomical  condition  of  old  age  in  man,  and  to 
indicate  to  you  further  that  the  study  merely  of  that 
anatomical  condition  is  not  enough  to  enable  us  to 
understand  the  problem  we  are  tackling,  but  that  we 
must  in  addition  extend  the  scope  of  our  inquiry  so 
that  it  will  include  animals  and  plants,  for  since  in  all 
of  these  living  beings  the  change  from  youth  to  old 
age  goes  on,  it  follows  that  we  can  hardly  expect  an 
adequate  scientific  solution  of  the  problem  of  old  age 
unless  we  base  it  on  broad  foundations.  By  such 
breadth  we  shall  make  our  conclusion  secure,  and  we 
shall  know  that  our  explanation  is  not  of  the  charac- 
ter of  those  explanations  which  I  indicated  to  you  in 
the  last  lecture,  which  are  so-called  "  medical,"  and  are 
applicable  only  to  man,  but  rather  will  our  explanation 
have  in  our  minds  the  character  of  a  safe,  sound,  and 
trustworthy  biological  conclusion.  The  problem  of 
age  is  indeed  a  biological  problem  in  its  broadest 
sense,   and  we  cannot  study,   as  we  now  know,  the 

38 


THE  CELLULAR   CHANGES  OF  AGE  39 

problem  of  age  without  including  in  it  also  the  con- 
sideration of  the  problems  of  growth  and  the  prob- 
lems of  death.  I  hope  to  so  entice  you  along  in  the 
consideration  of  the  facts  which  I  have  to  present, 
as  to  lead  you  gently  but  perceptibly  to  the  conclu- 
sion that  we  can  with  the  microscope  now  recognise 
in  the  living  parts  of  the  body  some  of  those  charac- 
teristics which  result  in  old  ao^e.  Old  agre  has  for  its 
foundation  a  condition  which  we  can  actually  make 
visible  to  the  human  eye.  As  a  step  towards  this 
conclusion,  I  desire  to  show  you  this  evening  some- 
thing in  regard  to  the  microscopic  structure  of  the 
human  body. 

We  now  know  that  the  bodies  of  all  animals  and 
plants  are  constituted  of  minute  units  so  small  that 
they  cannot  be  distinguished  by  the  naked  eye, 
although  they  can  be  readily  demonstrated  by  the 
microscope.-^  These  units  have  long  been  knov/n  to 
naturalists  by  the  name  of  cells.  The  discovery  of 
the  cellular  constitution  of  livinof  bodies  marks  one 
of  the  great  epochs  in  science,  and  every  teacher 
who  has  occasion  to  deal  in  his  lectures  with  the 
history  of  the  biological  sciences  finds  it  necessary  to 
dwell  upon  this  great  discovery.  It  was  first  shown 
to  be  true  of  plants,  and  shortly  after  likewise  of  ani- 
mals. The  date  of  the  latter  discovery  was  1839. 
We  owe  it   to  Theodor  Schwann,   whose  name  will 

^  I  have  estimated  the  average  diameter  of  the  cells  in  the  human  adult  as 
fifteen  thousandths  of  a  millimetre  (0.015  mm.).  One  millimetre  is  approxi- 
mately one  twenty-fifth  of  an  inch.  This  estimate  is  probably  not  exact,  but 
may  serve  to  indicate  the  order  of  cell  dimensions. 


^ 


/c 


Fig.  7.  Cells  from  the  Mouth  (Oral  Epithelium)  of  the  Sala- 
mander, to  show  the  phases  of  cell  division  or  mitosis.  The  cells  are  not 
represented  in  the  living  slate,  but  artificially  preserved  and  coloured.  In  the 
living  cell  there  is  no  such  marked  contrast  of  colour  between  the  protoplasm 
and  the  nucleus  as  appears  in  these  figures. — After  Sobotta, 

40 


THE  CELLULAR   CHANGES  OF  AGE  41 

therefore  ever  be  honoured  by  all  investigators  of  vital 
phenomena.  What  the  atom  has  been  to  the  chem- 
ist, the  cell  is  to  the  naturalist,  but  with  this  differ- 
ence, atoms  are  hypothetical,  cells  are  known  by 
direct  observation.  Every  cell  consists  of  two  essen- 
tial parts.  There  is  an  inner  central  kernel  which  is 
known  by  the  technical  name  of  nucleus,  and  a  cov- 
ering- mass  of  livingr  material  which  is  termed  the 
protoplas7n  and  constitutes  the  body  of  the  cell.  I 
will  now  call  for  the  first  of  our  lantern  slides  to  be 
thrown  upon  the  screen.  It  presents  to  you  pictures 
of  the  cells  as  they  are  found  lining  the  mouth  of  the 
European  salamander.  The  two  figures  at  the  top 
illustrate  very  clearly  the  elements  of  the  cell.  The 
protoplasm  forms  a  mass,  exhibiting  in  this  view  no 
very  distinctive  characteristics,  and  therefore  offering 
a  somewhat  marked  contrast  with  the  darker  oval 
nucleus,  which  presents  in  its  interior  a  number 
of  granules  and  threads.  Every  nucleus  consists 
of  a  membrane  by  which  it  is  separated  from  the 
protoplasm,  and  three  internal  constituents  :  First,  a 
network  of  living  material,  more  or  less  intermingled 
with  which  is  a  second  special  substance,  chromatine, 
which  owes  its  name  to  the  very  marked  affinity 
which  it  displays  for  the  various  artificial  colouring 
matters  which  are  employed  in  microscopical  re- 
search.^    The  third  of  the  internal  nuclear  constitu- 

'  It  seems  to  me  very  doubtful  whether  the  distinction  drawn  between  the 
network  and  the  chromatine  of  the  nucleus  is  valid — but  the  distinction  is 
usually  affirmed  in  the  text-books  of  to-day.     There  are  observations  whict 


42  AGE,  GROWTH,  AND  DEATH 

ents  we  may  call  the  sap  (hyaloplasma),  the  fluid 
material  which  fills  out  the  meshes  of  the  network. 
Later  on  we  shall  have  occasion  to  study  somewhat 
more  carefully  the  principal  variations  which  nuclei 
of  different  kinds  may  present  to  us,  and  we  shall 
learn  from  such  study  that  we  may  derive  some 
further  insight  into  the  rapidity  of  development  and 
the  nature  of  the  changes  which  result  in  old  age. 
While  the  picture  is  upon  the  screen,  I  wish  to  call 
your  attention  to  the  other  figures,  which  illustrate 
the  process  of  cell  multiplication.  As  you  regard 
them  you  will  notice  in  the  succession  of  illustrations 
that  the  nucleus  has  greatly  changed  its  appearance. 
The  substance  of  the  nucleus  has  gathered  into  sepa- 
rate peculiarly  elongated  granules,  each  of  which  is 
termed  a  chromosome.  The  chromosomes  are  very 
conspicuous  under  the  microscope,  because  they  ab- 
sorb artificial  stains  of  many  sorts  with  great  avidity 
and  stand  out  therefore  conspicuously  coloured  in 
our  microscopic  preparations.  They  are  much  more 
conspicuous  than  is  the  substance  of  the  resting 
nucleus.  The  fact  that  we  can  readily  distinguish 
the  dividing  from  the  resting  nucleus  under  the 
microscope, — compare  Fig.  72, — we  shall  take  advan- 
tage of  later  on,  for  it  offers  us  a  means  of  investigat- 
ing the  rate  of  growth  in  various  parts  of  the  body. 
I  should  like,  therefore,  to  emphasise  the  fact  at  the 
present  time  sufficiently  to  be  sure  that  it  will  remain 

render  it  probable  that  there  is  in  the  network  only  one  constituent  of  which 
the  chromatine  is  a  functional  modification,  varying  in  extent  in  accordance 
with  the  alternating  phases  of  cell-life. 


THE  CELLULAR  CHANGES  OF  AGE  43 

in  your  minds  until  the  final  lecture,  in  which  we  shall 
make  practical  use  of  our  acquaintance  with  it.  It  is 
unnecessary  for  our  purposes  to  enter  into  a  detailed 
description  of  the  complicated  processes  of  cell  di- 
vision. But  let  me  point  out  to  you  that  the  end  result 
is  that  where  we  have  one  cell  we  get  as  the  result  of 
division — two  ;  but  the  two  divided  cells  are  smaller 
than  the  mother  cell  and  have  smaller  nuclei.  They 
will,  however,  presently  grow  up  and  attain  the  size 
of  their  parent. 

Every  cell  is  a  unit  both  anatomically  and  physio- 
logically. It  has  a  certain  individuality  of  its  own. 
In  many  cases  cells  are  found  to  be  isolated  or  sepa- 
rated completely  from  one  another.  But,  on  the  other 
hand,  we  also  find  numerous  instances  in  which  the 
living  substance  of  one  cell  is  directly  continuous 
with  that  of  another.  When  the  cells  are  thus  re- 
lated, we  speak  of  the  union  of  cells  as  syncytium. 
Of  this  I  offer  you  an  illustration  in  the  second  picture 
upon  the  screen  (Fig.  8),  which  represents  the  em- 
bryonic connective  tissue  of  man.  In  this  you  can 
see  the  prolongations  of  the  protoplasm  of  a  single 
cell  body  uniting  with  the  similar  prolongations  from 
other  cell  bodies,  the  cells  themselves  thus  forming, 
as  it  were,  a  continuous  network  with  broad  meshes 
between  the  connecting  threads  of  protoplasm.  The 
spaces  or  meshes  are,  however,  not  entirely  vacant, 
but  contain  fine  lines  which  correspond  to  the  exist- 
ence of  fibrils,  which  are  characteristic  of  connective 
tissue,  and  at  the  stage  of  development  represented 


44 


AGE,  GROWTH,  AND  DEATH 


in  this  picture  are  beginning  to  appear.  It  is  fibrils 
of  this  sort  which  we  find  as  the  main  elements  in 
the  constitution  of  sinews  and  tendons,  as,  for  in- 
stance, the  tendon  of  Achilles,  at  the  heel.  In  a  very 
young  body  we  find  there  are  but  few  fibrils  ;  in  the 
adult  body  an  immense  number. 

If  we  are  to  be  scientifically  exact  we  must  note 


Fig.  8.  Example  of  a  Syncytium.  Embryonic  connective  tissue  from  the 
umbilical  cord  of  a  human  embryo  of  about  three  months,  magnified  about 
400  diameters  ;  c,  c,  cells  ;  f,  intercellular  fibrils. 

that  in  the  early  stages  of  vertebrates,  the  germ  or 
embryo  is  not  constituted  of  discrete  cells.  There 
are  nuclei,  and  each  nucleus  is  surrounded  by  proto- 
plasm. Each  nucleus  is  perfectly  individualised,  but 
its   protoplasm   merges    into   that    about    the    neigh 


THE  CELLULAR   CHANGES  OF  AGE  45 

bouring  nuclei.  All  the  primitive  parts  are  then 
true  syncytia.  Thus  it  happens  that  in  Fig.  9,  which 
represents  sections  of  a  very  young  rabbit  germ,  the 
single  cells  are  not  marked  off.  Nevertheless  it  is 
customary  and  convenient  to  speak  of  the  cells  even 
at  such  a  stage.  The  actual  delimitation  of  the  cells 
occurs  in  older  stages  in  nearly  every  part  of  the 
body.  The  blood  corpuscles  are  always  the  first  cells 
in  vertebrates  to  become  definitely  individualised. 

There,  is,  in  fact,  as  you  probably  all  know,  a  con- 
stant growth  of  cells ;  and  this  growth  implies  also, 
naturally,  their  multiplication.  There  has  been  in 
each  of  us  an  immense  number  of  successive  cell 
generations,  and  at  the  present  time  a  multiplication 
of  cells  is  going  on  in  every  one  of  us.  It  never 
entirely  ceases  as  long  as  life  continues.  The  de- 
velopment of  the  body,  however,  does  not  consist 
only  of  the  growth  and  multiplication  of  cells,  but 
also  Involves  changes  in  the  very  nature  of  the  cells, 
alterations  In  their  structure.  Cells  In  us  are  of  many 
different  sorts,  but  In  early  stages  of  development 
they  are  of  few  sorts.  Moreover,  In  the  earliest 
stages  we  find  the  cells  all  more  or  less  alike.  They 
do  not  differ  from  one  another.  Hence  comes  the 
technical  term  of  differentiation,  to  designate  the 
modifications  which  cells  undergo  with  advancing 
age.  Some  authorities  use  specification  as  a  tech- 
nical synonym  for  differentiation.  At  first  cells  are 
alike  ;  In  older  Individuals  the  cells  have  become  of 
different   sorts,   they  have   been    differentiated    Into 


46  AGE,  GROWTH,  AND  DEATH 

various    classes.      This    whole    phenomenon    of   cell 
change  is  comprehensively  designated  by  the  single 


i^-l'^    '^i^Si^^2S^I&' 


n  ' 

"^  -ok/t^V-    .     ,  -     -----  -     :>:^  ,v 


-"^?'®  SSi^feMsi^-*^^''^ 


i^^^  _~^  -'i-'-^-'--^^    ^^s^. 


Fig.  9.  Three  Transverse  Sections  through  a  Rabbit  Embryo  of 
Seven  and  One  Half  Days,  from  series  622  of  the  Harvard  Embryological 
Collection.  A,  section  247  across  the  anterior  part  of  the  germinal  area. 
B,  section  260  across  the  middle  region  of  the  germinal  area,  C,  section  381 
through  the  posterior  part  of  the  germinal  area.     Magnified  300  diameters. 

word,    cytomorphosis,    which    is     derived    from    two 
Greek  words    meaning  cell  and  foi^m,   respectively. 


THE  CELLULAR  CHANGES  OF  AGE  47 

A  correct  understanding  of  the  conception  cytomor- 
phosis  is  an  indispensable  preliminary  to  any  com- 
prehension of  the  phenomena  of  development  of 
animal  or  plant  structure.  I  shall  endeavour,  there- 
fore, now  to  give  you  some  insight  into  the  phenomena 
of  cytomorphosis  as  regarded  by  the  scientific  bio- 
logist. The  first  cells  which  are  produced  are  those 
which  form  the  young  embryo.  We  speak  of  them 
on  that  account  as  embryonic  cells,  or  cells  of  the 
embryonic  type.  Our  next  picture  illustrates  the 
actual  character  of  such  cells  as  seen  with  the  micro- 
scope, for  it  represents  a  series  of  sections  through 
the  body  of  a  rabbit  embryo,  the  development  of 
which  has  lasted  only  seven  and  one  half  days.  You 
will  notice  at  once  the  simplicity  of  the  structure. 
There  are  not  yet  present  any  of  those  parts  which 
we  can  properly  designate  as  organs.  The  cells  have 
been  produced  by  their  own  multiplication,  and  are 
not  yet  so  numerous  but  that  they  could  be  readily 
actually  counted.  They  are  spread  out  in  somewhat 
definite  layers  or  sheets,^  but  beyond  that  they  show 
no  definite  arrangement  which  is  likely  to  attract 
your  attention.  That  which  I  wish  you  particularly 
to  observe  is  that  in  every  part  of  each  of  these  sec- 

•  The  layers  are  three  in  number,  and  are  known  as  the  ger?n-layers;  the 
outer  layer  (uppermost  in  each  of  the  three  sections  in  Fig.  9)  is  the  ectoderm. 
the  middle  the  mesoderm,  and  the  inner  one  the  entodertn.  The  science  of 
embryology  has  for  its  chief  task  to  trace  the  numerous  modifications  and  often 
very  complicated  metamorphoses  which  the  three  simple  germ-layers  pass 
through  in  order  to  produce  the  complex  organs  of  the  adult.  Our  present 
conceptions  of  the  structure  of  multicellular  animals  are  based  on  two  great 
discoveries,  first  of  the  germ-layers,  second  of  cells. 


48 


AGE,  GROWTH,  AND  DEATH 


^^■'-.  €a-\ 


><S2> 


tions  the  cells  appear  very  much  alike.  The  nuclei  are 
all  similar  in  character,  and  for  each  of  them  there  is 
more  or  less  protoplasm  ;  but  the  protoplasm  in  all 
parts    of    these  young   rabbits   is   found   to   be   very 

similar ;  and  indeed  if  we 
should  pick  out  one  of  these 
cells  and  place  it  by  itself  un- 
der the  microscope,  it  would 
be  impossible  to  tell  what  part 
of  the  rabbit  embryo  it  had 
been  taken  from,  so  much  do 
all  the  cells  of  all  the  parts 
resemble  one  another.  We 
learn  from  this  picture  that  the 
^r"<^~^^^M^~^ZZA      embryonic  cells  are  all  very 

much  alike,  simple  in  charac- 
ter, have  relatively  large  nu- 
clei, and  only  a  moderate 
amount  of  protoplasm  for 
each  nucleus  to  complete  the 
cell. 

Very  different  is  the  con- 
dition of  affairs  which  we  find 
when  we  turn  to  the  micro- 
scopic examination  of  the 
adult.      Did    time  permit    it 

corresponds  to  the  inner  surface      ^q^M    be     pOSsiblc    tO    Study 
of  the  tube.  .  ^  , 

a  succession  ot  stages  and 
show  you  that  the  condition  which  we  are  about  to 
study  as  existing  actually  in  the  adult  is  the  result  of  a 


FiG.  lo.  Portion  of  a 
Transverse  Section  of  the 
Spinal  Cord  of  a  Human  Em- 
bryo OF  Four  Millimetres. 
Harvard  Embryological  Collec- 
tion, series  714.  The  spinal  cord 
at  this  stage  is  a  tubular  struc- 
ture. The  figure  shows  a  por- 
tion of  the  wall  of  the  tube  ;  the 
left-hand  boundary  of  the  figure 


THE   CELLULAR   CHANGES  OF  AGE  49 

gradual  progress  and  that  in  successive  stages  of  the 
individual  we  can  find  successive  stages  of  cell  change; 
but  it  will  suffice  for  our  immediate  purpose  to  consider 
the  results  of  differentiation  as  they  are  shown  to  us  by 
the  study  of  the  cells  of  the  adult.  I  will  have  thrown 
upon  the  screen  for  you  a  succession  of  pictures  illus- 
trating various  adult  structures.  The  first  is,  how- 
ever, a  part  of  a  cross-section  of  the  embryonic  spinal 
cord  in  which  you  can  see  that  much  of  the  simple  char- 
acter of  the  embryonic  cells  is  still  kept.  All  parts 
of  the  spinal  cord,  as  the  picture  shows,  are  very  much 
alike,  and  the  nuclei  of  the  cells  composing  the  spinal 
cord  at  this  stage  are  all  essentially  similar  in  appear- 
ance. What  a  contrast  this  forms  with  our  next 
picture,  which  shows  us  an  isolated  so-called  motor 
nerve  cell  from  the  adult  spinal  cord.  It  owes  its 
name  motor  to  the  fact  that  it  produces  a  nerve  fibre 
by  which  motor  impulses  are  conveyed  from  the 
spinal  cord  to  the  muscles  of  the  body.  The  cell  has 
numerous  elongated  branching  processes  stretching 
out  in  various  directions,  but  all  leading  back  towards 
the  central  body  in  which  the  nucleus  is  situated. 
These  are  the  processes  which  serve  to  carry  in 
the  nervous  impulses  from  the  periphery  towards  the 
centre  of  the  cell,  impulses  which  in  large  part,  if  not 
exclusively,  are  gathered  up  from  other  nerve  cells 
which  act  on  the  motor  element.  At  one  point  there 
runs  out  a  single  process  of  a  different  character.  It 
is  the  true  nerve  fibre,  and  forms  the  axis,  as  it  was 
formerly  termed,  or   axon,  as  it  is  at    present    more 


5° 


AGE,  GROWTH,  AND  DEATH 


usually  named, 
of  the  nerve  fi- 
bre as    we  en- 
counter it  in  an 
ordinary  nerve. 
This    single 
thread-like  prolong- 
ation   of  the    nerve 
cell  is  likewise  con- 
stituted  by  the  liv- 
ing protoplasm  and 
serves  to  carry  the 
impulses  away  from 
the    cell    body    and 
transmit    them     ul- 
timately to  the  mus- 
cle  fibres  which  are 
to  be  stimulated  to 
contraction.     In  the 
embryonic   spinal 
cord  none  of  these 
processes      existed, 
and  the  amount   of 
the    protoplasm    in 
the    nerve    cell  was 
very  much    smaller. 
As  development  pro- 
gressed, not  only  did 
the  protoplasm  body 
grow,  but  the  processes  gradually  grew  out.      Some  of 


Fig.  II.  Copy  of  the  Original  Figure 
FROM  THE  Memoir  of  Deiters,  in  which  the 
proof  of  the  origin  of  the  nerve  fibres  directly 
from  the  nerve  cells  was  first  published.  The 
memoir  is  one  of  the  classics  of  anatomy.  It 
was  issued  posthumously,  for  the  author  died 
young,  to  the  great  loss  of  science.  The  figure 
represents  a  single  isolated  motor  nerve  cell 
from  the  spinal  cord  of  an  ox.  The  single 
unbranched  axon,  Ax,  is  readily  distinguished 
from  the  multiple  branching  dendrites,  Deii. 
Nu  is  the  spherical  nucleus  with  its  charac- 
teristic central  dot. 


THE  CELLULAR   CHANGES  OF  AGE 


51 


them  branched  so  as  to  better  receive  and  collect  the 
impulses  ;  one  of  them  remained  single  and  very  much 
elongated,  and  acquired  a  somewhat  different  structure 
in  order  to  serve  to  carry  the  nervous  impulses  away. 
The  third  picture^  shows  us   a   section   through   the 


Fig.  12.  A  Large  Cell  from  the  Small  Brain  (Cerebellum)  of  a 
Man.  It  is  usually  called  a  Purkinje's  cell.  It  was  stained  black  throughout 
by  what  is  known  as  the  Golgi  silver  method,  hence  shows  nothing  of  its 
internal  structure. — After  von  Kolliker. 


Spinal  cord  of  an  adult  fish.  It  has  been  treated  by  a 
special  stain  in  order  to  show  how  certain  elements  of 
the  spinal  cord  acquire  a  modification  of  their  organisa- 
tion by  which  they  are  adapted  to  serve  as  supports 
for  the  nervous  elements  proper.     They  play  in  the 

*  The  illustration  referred  to  is  not  reproduced  in  the  text. 


52  AGE,  GROWTH,  AND  DEATH 

microscopic  structure  the  same  supporting  role  which 
the  skeleton  performs  in  the  gross  anatomy  of  the 
body  as  a  whole.  They  do  not  take  an  active  part 
in  the  nervous  functions  proper.  None  of  the  ap- 
pearances which  this  figure  offers  for  our  considera- 
tion can  be  recognised  in  any  similar  preparation  of 
the  embryonic  cord.  Obviously,  then,  from  the  em- 
bryonic to  the  adult  state  in  the  spinal  cord  there 
occurs  a  great  differentiation.  That  which  was  alike 
in  all  its  parts  has  been  so  changed  that  we  can  readily 
see  that  it  consists  of  many  different  parts.  A  strik- 
ing illustration  of  this  is  afforded  by  the  next  picture, 
which  represents  one  of  the  large  nerve  cells  which 
occur  in  the  small  brain,  or  cerebellum,  that  portion 
of  the  central  nervous  system  which  the  physiologists 
have  demonstrated  to  be  particularly  concerned  in  the 
regulation  and  co-ordination  of  movements.  These 
large  cells  occur  only  in  this  portion  of  the  brain,  and 
as  you  see,  differ  greatly  in  appearance  from  the 
motor  cells  of  the  type  which  we  were  considering  a 
few  moments  ago.  And,  again,  another  picture  illus- 
trates yet  other  peculiarities  of  the  adult  nerve  cells. 
The  upper  figures  in  this  plate  are  taken  from  cells 
which  have  been  coloured  uniformly  of  a  very  dark 
hue,  in  consequence  of  which  they  are  rendered  so 
opaque  that  the  nucleus  which  they  really  contain  is 
hidden  from  our  view.  But  the  deep  artificial  colour 
makes  it  easy  to  follow  out  the  form  of  the  cells  and 
the  ramifications  of  their  long  processes.  In  the 
middle  figures  we  have  cells  which  have  been  stained 


rig.l. 


A;/ 


# 


1^ 


^     r^ 
(^ 

}' 

'^m 

v^ 

lill 

iit-^ 

F  1(1.3. 

Fiij.4. 

Fiff.  J 

..J 

FIG.  13.     Various  Kinds  of  Human  Nerve  Cells,  as  Described  in  the 

Text. — After  Sobotta. 

53 


54  AGE,  GROWTH,  AND  DEATH 

by  another  method  which  brings  out  very  clearly  to 
the  eye  the  fact  that  in  the  protoplasm  of  the  cell 
there  are  scattered  spots  of  substance  of  a  special 
sort.  No  such  spots  can  be  demonstrated  in  the 
elements  of  the  young  embryonic  nerve  cells.  To 
some  fanciful  observers  the  spots,  thus  microscopically 
demonstrable  in  the  nerve  cells,  recall  the  spots  which 
appear  on  the  skin  of  leopards,  and  hence  they  have 
bestowed  upon  these  minute  particles  the  term  tigroid 
substance.  The  bottorn  figures  represent  the  kind  of 
nerve  cells  which  occur  upon  the  roots  of  the  spinal 
nerves,  and  each  of  which  is  surrounded  by  a  special 
protective  envelope  of  small  non-nervous  cells.  It  is 
unnecessary  to  dwell  upon  their  appearance,  as  the 
mere  inspection  of  the  figures  shows  at  once  that  they 
differ  very  much  indeed  from  the  other  nerve  cells 
we  have  considered. 

We  pass  now  to  another  group  of  structures,  the  tis- 
sues which  are  known  by  the  technical  name  of  epithe- 
lia.  You  can  notice  immediately  in  the  figures  on  the 
plate  (Fig.  14)  that  the  appearances  are  very  different 
from  those  we  have  encountered  in  contemplating  the 
cells  of  the  nervous  system,  and  you  can  readily  satisfy 
yourselves,  by  the  comparison  of  the  various  figures 
now  before  you,  of  the  further  fact  that  these  epithelia 
are  unlike  one  another.  The  figures  represent  epi- 
thelium, respectively,  first  from  the  human  ureter ; 
second,  from  the  respiratory  division  of  the  human 
nose  ;  third,  from  the  human  ductus  epididymidis  ;  and, 
fourth,  from  the  pigment  layer  of  the  retina  of  the  cat. 


I'ic/.l. 


vjgiva^  --    ^grjBW', 


%.^. 


/>y.j. 


/'V_^.  4 


Fig.  14.  Sections  of  Four  Sorts  of  Epithelium,  i,  from  the  human 
ureter,  X  450  diams.;  2,  stratified  ciliated  epithelium  from  the  respiratory 
region  of  the  human  nose,  X  500  diams. ;  3,  ciliated  epithelium  from  the  human 
ductus  epididymidis,  X  420  diams.;  4,  surface  view  of  the  pigmented  epithelium 
from  the  retina  of  a  cat's  eye,  X  280  diams. — After  Sobotta. 

55 


56 


AGE,  GROWTH,  AND  DEATH 


We  turn  now  to  a  representation  of  a  section  of 
one  of  the  orbital  glands.  This  is  very  instructive 
because  we  see  not  only  that  the  cells  which  compose 
the  gland  have  acquired  a  special  character  of  their 
own,  but  also  that  they  are  not  uniform  in  their  ap- 
pearances. This  lack  of  uniformity  is  due  chiefly  to 
the  fact  that  the  cells  change  their  appearance  accord- 
ing to  their  functional  state.  We  can  actually  see  in 
these  cells  under  the  microscope  the  material  im- 
bedded in  their  protoplasmic  bodies  out  of  which  the 


A  B 

Fig.  15.  To  Show  the  Orbital  Gland  of  a  Dog.  A ,  with  the  material  to 
form  the  secretion  accumulated  within  the  cells.  B,  after  loss  of  the  material 
through  prolonged  secretion. — From  R.  Heidenhain  after  Lavdowsky. 

secretion,  which  is  to  be  poured  forth  by  the  cells,  is 
to  be  manufactured.  So  long  as  that  material  for 
the  secretion  is  contained  in  the  cells,  the  cells  appear 


THE   CELLULAR   CHANGES  OF  AGE  57 

large,  and  their  protoplasmic  bodies  do  not  readily 
absorb  certain  of  the  staining  matters  which  the 
microscopist  is  likely  to  apply  to  them  (Fig.  15,  A). 
When,  however,  the  accumulated  raw  material  has 
been  changed  into  the  secretion  and  discharged  from 
the  gland,  the  cell  is  correspondingly  reduced  in  bulk, 
and  as  you  see  (Fig.  15,  B),  it  then  takes  up  the  stain 
with  considerable  avidity,  as  does  also  the  nucleus, 
which  has  likewise  become  reduced  in  size.  These 
facts  are  very  instructive  for  us,  since  they  prove 
conclusively  that  with  the  microscope  we  can  see  at 
least  part  of  the  peculiarities  in  cells  which  are  cor- 
related with  their  functions.  We  can  actually  observe 
that  the  cells  of  the  orbital,  and,  it  might  be  added,  of 
the  salivary,  glands  are  able  to  produce  their  peculiar 
secretion  because  they  contain  a  kind  of  substance 
which  in  the  embryonic  cell  does  not  appear  at  all. 
There  is  a  visible  differentiation  of  the  orbital-gland 
cells  from  the  simple  stage  of  the  embryonic  cells. 
Something  similar  to  this  can  be  recognised  in  the 
next  of  our  pictures  representing  sections  of  the 
gland  properly  known  as  the  pancreas  but  which  is 
sometimes  termed  the  abdominal  salivary  gland  for 
the  reason  that  it  somewhat  resembles  the  true 
salivary.  In  the  cells  of  the  pancreas  also  we  can  see 
the  material  which  is  to  produce  the  secretion  ac- 
cumulated in  the  inner  portion  of  the  cell,  and  when 
it  is  so  accumulated  the  cell  appears  enlarged  in  size 
and  the  nucleus  is  driven  back  towards  the  outer  end 
of  the  cell  where  some  unaltered  protoplasm  is  also 


58  AGE,  GROWTH,  AND  DEATH 

accumulated  (Fig.  i6,  A^.  When  this  raw  material  is 
turned  over  into  secretion  by  a  chemical  change,  it  is 
discharged  from  the  cell,  the  cell  loses  in  volume,  and  in 
its  shrunken  state  presents  a  very  different  appearance, 
as  is  shown  at  B  in  the  figure.     It  is  necessary  for  the 


Fig.  i6.  Two  Sections  of  the  Pancreatic  Gland  of  a  Dog.  A,  the 
cells  are  enlarged  by  the  accumulation  of  material  to  form  the  secretion.  B, 
the  cells  are  shrunk  because  there  has  been  prolonged  secretion  and  part  of 
their  substance  is  lost. — From  R.  Heidenhain. 

cells  to  again  elaborate  the  material  for  secretion  be- 
fore they  can  a  second  time  become  functionally  active. 
Here  we  have  something  of  the  secret  of  the  produc- 
tion of  the  various  juices  in  the  body  revealed  to  us. 
Other  excellent  examples  of  the  differentiated  con- 
dition of  the  cells  are  afforded  us  by  the  examination 


THE  CELLULAR    CHANGES  OF  AGE  59 

of  hairs,  of  which  I  will  show  you  two  pictures.     The 


Fig.  17.  Section  of  the  Human  Skin,  Made  so  that  the 
Hairs  are  Cut  Lengthwise.  ^/,  erector  muscle  of  the  hair  ; 
ep,  epidermis ;  c,  deep  skin  or  dermis  ;  /J>,  hair  follicle  ;  J?p,  root  of 
hair  ;  J?c,  subdermal  tissue  ;  gls,  sweat  glands  ;  Cap,  fibrous  layer 
(aponeurosis).     X  15  diameters. — After  Sobotta. 

first   represents   a   section   through   the    human   skin 
taken  in  such  a  way  that  the  hairs  are  themselves  cut 


6o  AGE,  GROWTH,  AND  DEATH 

lengthwise  and  you  see  not  only  that  each  hair  con- 
sists of  various  parts,  but  also  that  the  cells  in  these 
parts  are  unlike.  The  follicles  within  the  skin  in 
which  the  hair  is  lodged  likewise  have  walls  with  cells 
of  various  sorts.  It  may  interest  you  also  to  point 
out  in  the  figure  the  little  muscle,  Ap,  which  runs 
from  each  hair  to  the  overlying  skin,  so  disposed  that 
when  the  muscle  contracts  the  "particular  hair  will 
stand  up  on  end."  Still  more  clearly  does  the  variety 
of  cells  which  actually  exists  in  a  hair  show  in  the 
following  picture  (Fig.  i8),  which  represents  a  cross- 
section  of  a  hair,  and  its  follicle,  but  more  highly 
magnified  than  were  the  hairs  in  the  previous  figure. 
The  adult  body  consists  of  numerous  organs. 
These  are  joined  together  and  kept  in  place  by  inter- 
vening substance.  The  organs  themselves  consist 
of  many  separate  parts  which  are  also  joined  by  a 
substance  which  keeps  them  in  place.  This  sub- 
stance has  received  the  appropriate  name  of  connec- 
tive tissue.  We  find  in  the  adult  that  it  consists  of  a 
considerable  number  of  structures.  There  are  cells 
and  fibres  of  more  than  one  kind,  which  have  been 
produced  by  the  cells  themselves.  There  is  more  or 
less  substance  secreted  by  the  cell  which  helps  to  give 
consistency  to  the  tissue.  In  some  cases  this  sub- 
stance, which  is  secreted  by  the  cells,  becomes  tougher 
and  acquires  a  new  chemical  character.  Such  is 
the  case,  for  instance,  with  cartilage.  Or,  again,  you 
may  see  a  still  greater  chemical  metamorphosis  going 
on  in  the  material  secreted  by  the  cells  in  the  case 


THE  CELLULAR  CHANGES  OF  AGE 


6i 


of  bone,   where  the  substance   Is  made  tougher  and 
stronger  by  the  deposit  of  calcareous  material.      No- 


^  »  *  r"^  *  #  5>  ^_ 


\ 


**. 


w 


/.y 


Fig.  i8.  Cross  Section  of  the  Root  of  a  Hair,  hbl,  longitudinal,  hbr, 
circular  fibres  of  the  hair  sheath  ;  bg,  blood-vessels  ;  gl,  hyaline  sheath  ;  aiv, 
outer  layer  of  follicle  ;  i^v,  inner  layer  of  follicle  ;  r,  outer  cuticle  of  the  hair; 
7,  Huxley's  layer  of  the  follicle  ;  2,  Henle's  layer  of  the  follicle.  X  3oo  diame- 
ters.— After  Sobotta. 


thino-  like  cartilao-e,  nothino-  like  bone,  exists  in  the 


62 


AGE,  GROWTH,  AND  DEATH 


early  state  of  the  embryo.    They  represent  something 
different  and  new. 

The    next    of   our  illustrations,   Figs.    19  and  ^o, 

show   us  muscle   fibres  of  the 

sort  which  serve  for  our  volun- 

tarymotions 

and       are 

connected 

ty  p  ically 

with     some 

part   of  the 

skele  t  o  n  . 

These  mus- 

clehbresare 

elongated 

structures. 

Each    fibre 

contains     a 

contractile 

substance 
different  from  protoplasm,  and 
which  exists  in  the  form  of  delicate 
fibrils  which  run  lengthwise  in  the 
muscle  fibres  (Fig.  19),  and  is  so 
disposed,  further,  that  a  series  of 
fine  lines  are  produced  across  the 
fibre  itself  (Fig.  20),  each  line  cor- 
responding with  a  special  sort  of 
material  different  from  the  original 
protoplasm.   These  cross  lines  give  to   the   voluntary 


Fig.  19.  Cross  Section 
OF  A  Lingual  Muscle  Fibre 
OF  THE  Mocassin  Snake,  An- 

CISTRODON  PiSCIVORUS.       The 

single  large  dark  spot  repre- 
sents a  nucleus.  Each  small 
dot  represents  a  cross  section 
of  a  muscle  fibril.  There  are 
several  hundred  in  each   fibre. 


,1 

Fig.  20.  Part  OF  a 
Muscle  Fibre  of  the 
Human  Tongue  to 
Show  the  Cross  Stri- 
ations.  Two  nuclei 
are  included,  one  of 
which  is  shown  at  the 
edge  of  the  fibre,  the 
other  in  surface  view. 
In  the  adult  striated 
muscle  fibres  of  mam- 
mals the  nuclei  are  su- 
perficially placed. 


THE  CELLULAR  CHANGES  OF  AGE 


63 


muscle  fibres  a  very  characteristic  appearance,  in 
consequence  of  which  they  are  commonly  desig- 
nated in  scientific  treatises  by  the  term  striated.  A 
striated  muscle  fibre  is  that  which  is  under  the  con- 


Blood-ves- 
sels. 


Nucleus. 


Nucleus. 


Inner      sur- 
face  of  the 
retina      (to- 
ward    the 
light). 


Blood-vessels. 

Fig.  21.  Section  of  a  Human  Retina,  from  Stohr's  Histology,  sixth 
American  edition.  Although  the  retina  is  very  thin  it  comprises  no  less 
than  twelve  distinct  layers  ;  the  outermost  layer  is  highly  vascular.  The  pig- 
ment layer  prevents  the  escape  of  light.  The  rods  and  cones  convert  the  light 
waves  into  a  sensory  impulse,  which  is  transmitted  through  the  remaining 
layers  of  the  retina  to  the  optic  nerve.  The  total  structure  is  extremely 
complicated. 

trol  of  our  will.  It  should  perhaps  be  mentioned  that 
the  muscle  fibres  of  the  heart  are  also  striated,  though 
they  differ  very  much  in  other  respects  from  the 
true  voluntary  muscles. 

Last  of  all  for  this  series  of  demonstrations,  I  have 


64  AGE,  GROWTH,  AND  DEATH 

chosen  a  section  of  the  retina  (Fig.  21).  One  can  see 
near  the  top  of  the  figure  the  pecuHar  cyhndrical  and 
tapering  projections  (rods  and  cones)  which  are 
characteristic  of  a  retina,  projections  which  are  of 
especial  interest  because  they  represent  the  apparatus 
by  which  the  rays  of  Hght  are  transformed  into  an 
actual  sensory  perception.  After  this  has  been  ac- 
complished, the  perception  is  transmitted  into  the  in- 
terior substance  of  the  retina,  and  by  the  complication 
of  the  figure  you  may  judge  a  little  of  the  complica- 
tion of  the  arrangements  by  which  the  transmission 
through  this  sensory  organ  is  achieved,  until  the 
perception  is  given  off  to  a  nerve  fibre  and  carried  to 
the  brain.  There  is  not  time  to  analyse  all  I  might 
present  to  you  of  our  present  knowledge  concerning 
the  structure  of  the  retina.  But  it  will,  I  think,  suf- 
fice for  purposes  of  illustration  to  call  your  attention 
to  the  complicated  appearance  of  the  section  as  a 
whole  and  to  assure  you  that  nothing  of  the  sort 
exists   in   the  early  stage   of  the   embryo. 

To  recapitulate,  then,  what  we  have  learned  from 
the  consideration  of  these  pictures,  we  may  say  that 
in  place  of  uniformity  we  now  have  diversity.  It 
should  be  added,  to  make  the  story  complete,  that 
the  establishment  of  this  diversity  has  been  gradually 
brought  about,  and  that  what  we  call  development  is 
in  reality  nothing  more  than  the  making  of  diversity 
out  of  uniformity.  It  is  a  process  of  differentiation. 
Differentiation  is  indeed  the  fundamental  phenome- 
non of  life  ;  it  is  the  central  problem  of  all  biological 


THE  CELLULAR  CHANGES  OF  AGE  65 

research,  and  if  we  understood  fully  the  nature  of 
differentiation  and  the  cause  of  it,  we  should  have 
probably  got  far  along  towards  the  solution  of  the 
final  problem  of  the  nature  of  life  itself. 

The  size  of  animals  deserves  a  few  moments  of  our 
time,  for  it  is  intimately  connected  with  our  problem 
of  growth  and  differentiation.  Cells  do  not  differ 
greatly  from  one  another  in  size.  The  range  of  their 
dimensions  is  very  limited.  This  is  particularly  true 
of  the  cells  of  any  given  individual  animal.  Recent 
careful  investigations  have  been  made  upon  the  rela- 
tion of  the  size  of  cells  to  the  size  of  animals,  and  it 
has  been  found  that  animals  are  not  larger,  one  than 
another,  because  their  cells  are  larger,  but  because 
they  have  more  of  them.^  This  statement  must 
be  understood  with  certain  necessary  reservations. 
There  are  some  kinds  of  animals,  like  the  star-fish, 
which  have  very  small  cells  ;  others,  like  frogs  and 
toads,  which  have  large  cells  ;  so  that  a  star-fish  of 
the  same  bulk  as  a  given  frog  would  contain  a  great 
many  more  cells.  Our  statement  is  true  of  allied 
animals.  For  example,  a  large  frog  differs  from  a 
small  frog  or  a  large  dog  from  a  small  dog  by  the 
number  of  the  cells.  An  important  exception  to  this 
law  is  offered  for  our  consideration  by  the  cells  of 
the  central  nervous  system,  the  nerve  cells  properly 

'  G.  Levi,  "  Vergleichende  Untersuchungen  ueber  die   Grosse  der  Zellen," 
Verhandl.  Anat.  Ges.,  xix.,  156-158. 

G.  Levi,  "  Studi  sulla  Grandezza  delle  ceWvile,"  A 7'ckivio  ital.  anat.  embriol., 
v.,  pp.  291-358.     This  paper  is  important  and  suggestive. 
S 


84.1x71.r> 


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60.7x50.3  ,^.aOx54.0  44..^.x30.4 


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37.«x:kV.7  3<-..fixL*2.J>  .'Jl. 5x28.0 


Fig.  22.  Motor  Nerve  Cells  of  Various  Mammals,  all  from  the  cervical 
region  of  the  spinal  cord.  The  cells  are  represented  all  uniformly  magnified. 
The  cross  lines  on  each  figure  indicate  the  directions  in  which  the  original  cells 
have  been  measured. — After  Irving  Hardesty. 


66 


THE   CELLULAR   CHANGES  OF  AGE  67 

so  called.^  This  Is  demonstrated  by  the  slide  now  be- 
fore us  (Fig.  22),  which  shows  corresponding  motor 
nerve  cells  from  the  spinal  cords  of  twelve  different 
mammals  arranged  in  the  order  of  their  size — the  ele- 
phant, the  cow,  the  horse,  man,  the  pig,  the  dog,  the 
baboon,  the  cat,  the  rabbit,  the  rat,  the  mouse,  and  a 
small  bat.  You  recognise  immediately  that  there  is 
a  proportion  between  the  size  of  these  cells  and  the 
size  of  the  respective  species  of  animals.  To  a  minor 
degree,  but  much  less  markedly,  there  is  a  difference 
in  the  calibre  and  length  of  the  striated  or  voluntary 
muscle  fibres.  But  with  these  exceptions  our  state- 
ment is  very  nearly  exactly  true,  that  the  difference 
in  size  of  animals  does  not  involve  a  difference  in  the 
size  of  their  cells.  For  the  purpose  of  the  study  of 
development,  which  we  are  to  make  in  these  lectures, 
this  uniformity  in  the  size  of  cells  is  a  great  advan- 
tage, and  enables  us  to  speak  in  general  terms  in 
regard  to  the  growth  of  cells,  and  renders  it  superflu- 
ous to  stop  and  discuss  for  each  part  of  the  body 
the  size  of  the  cells  which  compose  it,  or  to  seek  to 
establish  different  principles  for  different  animals 
because  their  cells  are  not  alike  in  size. 

Now  we  pass  to  a  totally  different  aspect  of  cell 
development,  that  which  is  concerned  with  the  degen- 
eration of  cells.  For  we  find  that,  after  the  differ- 
entiation has  been  accomplished,  there  is  a  tendency 

'  Irving  Hardesty,  "  Observations  on  the  Medulla  Spinalis  of  the  Elephant, 
with  Some  Comparative  Studies  of  the  Intumescentia  Cervicalis  and  the 
Neurones  of  the  Columna  Anterior,"  Journ.  Co77ip.  Neurol.,  xii,  125-182, 
pis.  ix-xiii. 


68 


AGE,  GROWTH,  AND  DEATH 


to  carry  the  change  yet  further  and  to  make  it  so 
great  that  it  goes  beyond  perfection  of  structure,  so 
far  that  the  deterioration  of  the  cell  comes  as  a  con- 
sequence. Such  cases  of  differentiation  we  speak  of 
as  a  degeneration,  and  it  may  occur  in  a  very  great 


Fig.  23.  Group  of  Five  Nerve  Cells 
FROM  THE  First  Cervical  Ganglion  of  a 
Child  at  Birth.  Specimen  preserved  with 
osmic  acid.  X  500  diams. — After  C.  F. 
Hodge. 

number  of  ways.  Very  frequently  it  comes  about 
that  the  alteration  in  the  structure  of  the  cell  goes  so 
far  in  adapting  it  to  a  special  function  that  it  is  un- 
able to  maintain  itself  in  good  physiological  condition, 
and  failing  to  keep  up  its  own  nourishment  it  under- 
goes a  gradual  shrinkage  which  we  call  atrophy.  A 
very  good  illustration  of  this,  and  a  most  important 


THE  CELLULAR   CHANGES  OF  AGE 


69 


one,  is  offered  us  by  the  changes  which  go  on  in  the 
nerve  cells  in  extreme  old  age.  This  is  beautifully 
illustrated  by  the  two  pictures  which  are  now  before 


Fig,  24.  Group  of  Four  Nerve  Cells  from  the 
First  Cervical  Ganglion  of  a  Man  Dying  of  Old 
Age  at  Ninety-two  Years.  Specimen  preserved  with 
osmic  acid.  C,  C,  two  cells  still  intact,  but  loaded  with 
pigment  granules  ;  c,  c,  two  cells  which  have  disinte- 
grated.     X  500  diams. — After  C.  F.  Hodge. 

us,  copied  from  investigations^  of  Professor  Hodge, 
of  Clark  University.  The  two  figures  represent 
human   nerve  cells  taken  from  the  root  of  a  spinal 

'  C.  F.   Hodge,    "  Changes  in  Ganglion  Cells  from  Birth  to  Senile  Death," 
J  our  7ial  of  Physiol.^  vol.  xvii.,  pp.  129-134. 


70  AGE,  GROWTH,  AND  DEATH 

nerve.  The  first  figure  shows  these  cells  as  they 
exist  in  their  first  maturity ;  the  second  figure, 
as  they  appear  in  a  person  of  extreme  old  age. 
In  the  latter  you  will  readily  notice  that  the  cells,  C, 
have  shrunk  and  no  longer  fill  the  spaces  allotted  to 
them,  the  nuclei  have  become  small,  and  have  lost 
their  conspicuous  granules,  and  the  protoplasm  has 
changed  its  appearance  very  strikingly  because  there 
have  been  deposited  in  it  granules  of  the  pigment 
which  impart  to  these  cells  an  appearance  very  differ- 
ent from  that  which  they  had  in  their  maturity  when 
their  functional  powers  were  at  their  maximum.  You 
will  notice  also  in  other  parts  of  the  second  figure 
that  the  atrophy  of  the  cells  has  led  on  to  their  disin- 
tegration (c,  c),  that  they  are  breaking  down,  being 
destroyed,  and  that  the  result  of  their  breaking  down 
will  ultimately  be  their  disappearance.  Thus  the 
atrophy  of  a  cell  may  lead  to  its  death.  The  other 
two  figures^  upon  the  screen  show  us  the  brain  of 
the  humblebee.  On  the  left  is  the  brain  of  the  bee 
in  the  condition  in  which  we  find  it  when  the  bee 
first  emerges  from  the  pupa  or  chrysalis.  The  cells 
are  then  in  a  fine  physiological  condition,  but  in  a 
few  weeks  at  most  the  bee  becomes  old  and  in  the 
space  which  belongs  to  each  cell  we  find  only  its 
shrunken  and  atrophied  remnants,  the  nucleus  greatly 
reduced  In  volume,  and  an  irregular  mass  of  protoplasm 
shrunk  together  around  it.  These  cells  have  likewise 
undergone  an  atrophy  and  are  on  their  way  to  death. 

'  The  two  figures  of  the  bee's  brain  are  not  reproduced  in  the  text. 


THE  CELLULAR  CHANGES  OF  AGE  71 

In  other  cases  we  find  that  there  is  a  change  going 
on  which  we  call  necrobiosis,  which  means  that  the 
cells  continue  to  live,  but  change  their  chemical 
organisation  so  that  their  substance  passes  from  a 
living  to  a  dead  state.  No  more  perfect  illustration 
of  this  sort  of  chang-e  can  be  found  than  that  which 
is  afforded  by  the  skin.  In  the  deep  layer  of  the 
outer  skin  are  the  living  and  growing  parts,  which  we 
all  know  from  experience  are  sensitive.  As  these 
multiply  some  of  them  move  up  towards  the  surface ; 
and  they  are  continually  shoved  nearer  and  nearer 
the  surface  by  the  growth  of  the  cells  underneath. 
They  finally  become  exposed  at  the  surface  by  the 
loss  of  the  superficial  cells  which  preceded  them. 
During  this  migration  the  protoplasm  of  each  cell, 
which  was  alive,  is  changed  chemically  into  a  new 
substance  which  we  call  keratin,  or  in  common  lan- 
guage, horny  substance.  Ultimately  the  cell  proto- 
plasm becomes  nothing  but  horny  substance  and  is 
absolutely  dead.  Here  life  and  death  play  together 
and  go  hand  in  hand.  Hence  the  term  necrobiosis, 
death  and  life  in  one. 

Another  form  of  deo^eneration  which  occurs  in 
many  cases  is  of  great  interest  because  it  seems  as  if 
the  cells  were  making  a  last  great  effort ;  and  their  final 
performance  is  one  of  enlargement.  They  become 
greater  in  size  than  before  ;  but  there  will  follow  a  disin- 
tegration of  these  cells  also  ;  and  they  break  down  and 
are  lost.  This  form  of  degeneration  is  termed  hyper- 
trophy,  and  represents  a  third  type,  as  I  have  stated. 


72  AGE,  GROWTH,  AND  DEATH 

In  all  parts  of  the  body  degenerative  changes  are 
going  on,  and  they  represent  collectively  a  third 
phase  in  the  cytomorphic  cycle.  But  there  is  yet 
one  more  phase,  which  is  needed  to  complete  the 
story,  namely  the  phase  of  the  death  and  final  re- 
moval of  the  cells.  The  degenerative  change,  when 
complete,  always  results  in  the  death  of  the  cell.  In 
many  cases  the  dead  material  is  removed  merely  by 
being  cast  off,  as  is  the  case  with  the  skin.  All  the 
scales  which  peal  off  from  the  outer  surface  of  our 
body  represent  little  scraps  or  clusters  of  cells  which 
are  entirely  dead ;  and  in  the  interior  of  the  body,  in 
the  intestinal  canal,  and  in  the  glands  of  the  stomach, 
we  find  cells  continually  dying,  dropping  off  from 
their  place  upon  the  walls,  and  being  cast  away.  Or 
if  we  examine  the  saliva  which  comes  from  the  mouth, 
we  detect  that  that  also  is  full  of  cells  which  have 
died  and  fallen  off  from  their  connection  with  the 
body  and  are  thus  removed.  ^  An  even  more  impor- 
tant method  of  the  removal  of  cells  is  by  a  chemical 
process  in  consequence  of  which  the  cells  are  dis- 
solved and  disappear  before  our  eyes,  very  much  as 
marble  may  disappear  from  sight  under  the  corrosive 
action  of  an  acid.  Indeed,  we  know  that  all  the 
parts  of  the  body,  so  far  as  they  are  alive,  produce 
within  themselves  a  ferment  which  has  a  tendency  to 

'  Two  kinds  of  cells  are  commonly  found  in  the  saliva,  the  first  are  cornified 
cells  sloughed  off  the  lining  epithelium  of  the  mouth,  the  second  are  salivary- 
corpuscles,  which  are  really  white  blood  corpuscles  (leucocytes)  that  have 
migrated  into  the  saliva  and  died.  Being  dead  they  have  enlarged  themselves 
by  the  imbibition  of  water. 


THE  CELLULAR  CHANGES  OF  AGE  73 

destroy  the  living  substance  itself.^  The  production 
of  these  destructive  agents  is  going  on  at  all  times, 
apparently,  in  all  parts  of  the  body  which  are  alive. 
A  striking  illustration  of  this  is  offered  in  the  stom- 
ach. The  digestive  juice  which  is  produced  in  the 
stomach  is  capable  of  attacking  and  destroying  living 
substance,  and  any  organic  material  suitable  for  food 
which  is  placed  in  the  stomach  will,  as  we  know,  be 
attacked  by  the  gastric  juices,  dissolved  to  a  certain 
extent  by  them,  and  so  destroyed.  Why  then  does 
the  gastric  juice  not  attack  the  stomach  itself?  This 
is  but  one  phase  of  the  problem  why  the  body  does 
not  continually  destroy  itself.  It  has  lately  been 
ascertained  by  some  ingenious  physiological  investiga- 
tions that  the  body  not  only  produces  the  destructive 
agents,  but  also  antagonists  thereto,  anti-compounds 
which  tend  to  prevent  the  activity  of  the  destroying 
factors.  The  whole  problem  is  one  of  great  interest 
and  importance  which  calls  for  very  much  further 
investigation  before  we  can  be  said  to  have  arrived 
at  a  clear  understanding  of  it.  But  it  helps  us  much 
in  our  conception  of  cytomorphosis  to  know  that  all 
portions  of  the  body  are  endowed  with  this  faculty  of 
destroying  themselves,  for  it  enables  us  to  understand 
how  it  is  possible  that  after  the  degeneration  of  a  cell 
it  will  be  dissolved  away.  It  is  merely  that  the 
agents  of  solution  which  are  ordinarily  held  at  bay 

^  This  remarkable  phenomenon  is  known  by  the  name  of  autolysis.  An  ex- 
cellent general  exposition  of  the  subject  has  been  made  by  Dr.  P.  A.  Levene 
of  the  Rockefeller  Institute  in  the  Harvey  Lectures,  19C5-6,  p.  73. 


74  AGE,  GROWTH,  AND  DEATH 

are  no  longer  restrained,  and  they  at  once  do  their 
work. 

There  is  another,  but  comparatively  rare,  mode  of 
cell  destruction.  The  cells  break  up  into  separate 
fragments,^  which  are  then  dissolved  by  chemical 
means  and  disappear,  by  the  method  of  histolysis 
above  described,  or  else  are  devoured  by  the  cells 
to  which  reference  was  made  in  the  first  lecture  and 
which  are  known  by  the  name  of  phagocytes,  and  to 
which  Metchnikoff  has  attributed  so  great  an  impor- 
tance. It  is  unquestionable  that  phagocytes  do  eat 
up  fragments  of  cells  and  of  tissues,  and  may  even 
attack  whole  cells.  But  to  me  it  seems  probable  that 
their  role  is  entirely  secondary.  They  do  not  cause 
the  death  of  cells,  but  they  feed  presumably  only 
upon  cells  which  are  already  dead  or  at  least  dying. 
Their  activity  is  to  be  regarded,  so  far  as  the  prob- 
lem of  the  death  of  cells  is  concerned,  not  as  in- 
dicating the  cause  of  death,  but  as  a  phenomenon  for 
the  display  of  which  the  death  of  the  cell  offers  an 
opportunity.  A  word  of  caution !  Let  me  state 
explicitly  that  the  death  of  cells  does  not  depend 
always  upon  their  completing  the  cytomorphic  cycle. 
Death  may  befall  a  young  cell  just  as  it  may  befall  a 
young  child.      I   think  it  probable  in  all  such  cases, 

3  The  best  known  case  of  fragmentation  is  that  of  the  red-blood  corpuscles. 
Vast  numbers  of  them  are  constantly  destroyed  at  the  close  of  their  cytomor- 
phosis  by  this  process,  which  has  been  studied  by  numerous  investigators 
chiefly  in  the  spleen  and  the  liver.  Another  noteworthy  illustration  of  this 
method  of  cell  destruction  was  discovered  by  Ranvier  ("  Des  clasmatocytes," 
Archives  V anatomie  niicrosc,  iii.,  122-139)  among  wandering  cells  which 
occur  in  the  connective  tissue  of  mammals, 


THE  CELLULAR  CHANGES  OF  AGE  75 

even  when  the  death  of  the  cells  is  normal  and  occurs 
in  the  regular  course  of  development,  that  the  cause 
of  the  cells'  death  is  extraneous  to  them,  not  intrinsic. 
The  subject  of  the  death  and  disintegration  of  cells 
is  an  exceedingly  complex  one,  and  might  well  occupy 
our  attention  for  a  long  time.  But  it  is  not  permis- 
sible to  depart  from  the  strict  theme  which  we  have 
before  us,  and  I  will  content  myself,  therefore,  with 
throwing  upon  the  screen  two  tables  ^  which  illustrate 

1  I.     Death  of  Cells 
First.     Causes  of  death. 

A.  External  to  the  organism  : 

(i)   Physical  (mechanical,  chemical,  thermal,  etc.). 
(2)  Parasites. 

B.  Changes  in  intercellular  substances  (probably  primarily  due  to  cells)  : 

(i)  Hypertrophy. 

(2)  Induration. 

(3)  Calcification. 

—  (4)  Amyloid  degeneration  (infiltration). 

C.  Changes  inherent  in  cells. 

Second.      Morphological  changes  of  dying  cells. 

A.  Direct  death  of  cells  : 

(i)  Atrophy. 

(2)  Disintegration  and  resorption. 

B.  Indirect  death  of  cells  : 

(i)  Necrobiosis  (structural  change  precedes  final  death). 
(2)  Hypertrophic  degeneration  (growth   and  structural   change  often 
with  nuclear  proliferation  precede  final  death). 
Third.       Removal  of  cells. 

A.  By  mechanical  means  (sloughing  or  shedding). 

B.  By  chemical  means  (solution). 

C.  By  phagocytes. 

II.  Indirect  Death  of  Cells. 
A.     Necrobiosis. 

(i)  Cytoplasmic  changes  : 

(a)  Granulation. 

(b)  Hyaline  transformation. 


76  AGE,  GROWTH,  AND  DEATH 

to  us  the  variations  in  the  death  of  cells  and  in  their 
modes  of  removal  which  are  known  at  the  present 
time.  These  tables  are  taken  from  a  lecture  which  I 
delivered  in  New  York  a  few  years  ago,  and  which 
was  subsequently  published.^  If  any  of  you  should 
care  to  make  a  closer  acquaintance  with  them  they 
are  therefore  readily  accessible  to  you. 

In  order  to  render  the  nature  of  cytomorphosis 
clearer  to  you  let  me  ask  your  attention  for  a  concrete 
example,  the  biological  history  of  the  red  blood  cor- 
puscles, minute  bodies,  which  in  man  are  normally  cup- 
shaped,^  as  they  are  in  various  other  mammals  also.     It 


{c)  Imbibition. 

{d)  Desiccation. 

{e)  Clasmatosis. 
(2)  Nuclear  changes  : 

{a)  Karyorhexis. 

{b)  Karyolysis. 
B.     Hypertrophic  degeneration.    , 
(i)  Cytoplasmic : 

{a)  Granular. 

{b)  Cornifying. 

{c)  Hyaline. 

(2)  Paraplasmic : 
(a)  Fatty. 

{b)  Pigmentary. 
{c)  Mucoid. 
{d)  Colloid,  etc. 

(3)  Nuclear  (increase  of  chromatin). 

'  "The  Embryological  Basis  of  Pathology,"  the  Middleton  Goldsmith  Lecture 
delivered  before  the  New  York  Pathological  Society,  March  26,  1901,  Science, 
xiii.,  481-498,  and  Boston  Med.  Sur.  Journal,  cxliv.,  295-305. 

It  was  in  the  course  of  this  lecture  that  the  law  of  cytomorphosis  was  first 
publicly  announced  and  formulated. 

*  The  form  usually  ascribed  to  them  is  that  of  a  biconcave  disc,  a  shape  which 
appears  to  be  a  post-mortem  artefact.     The  true  shape  was  first  proven  by 


THE  CELLULAR  CHANGES  OF  AGE  77 

may  interest  you  to  know  that  it  was  not  until  1902 
that  the  actual  shape  was  correctly  recognised.  The 
corpuscles  are  so  small  that  about  5,000,000  occur  in 
a  cubic  millimetre  of  blood.  The  picture  now  before 
us  illustrates  the  life  history  of  these  cells. ^  In  the 
earliest  stage  of  their  cytomorphosis  the  cells  have 
each  a  well  formed  nucleus,  Fig.  25,  No.  i,  with  a  min- 
imal amount  of  protoplasm  around  it,  indeed  the  pro- 
toplasmic envelope  is  so  exceedingly  thin  that  earlier 
observers  thought  the  corpuscles  began  as  naked 
nuclei  without  a  cell  body.^  In  the  next  stage,  No. 
2,  the  cell  body  has  grown  so  that  there  is  more  pro- 
toplasm than  before  in  proportion  to  the  volume  of 
the  nucleus.  The  cell  body  around  the  nucleus  is  at  this 
time  loading  itself  with  haemoglobin,  the  red  substance 
which  plays,  as  you  all  know,  so  important  a  part  In 
respiration.   The  enlargement  of  the  cell  soon  reaches 

Weidenreich  {Archiv  f.  mikrosk.  Anat.,  LXI.,  p.  6i),  whose  observations  have 
been  confirmed  in  my  laboratory,  especially  by  Professor  F.  T.  Lewis  {Journ. 
Med.  Research,  x.,  513,  1904). 

'  As  regards  the  drawings  in  Figure  25,  it  should  be  stated  that  from  each 
embryo  a  single  corpuscle  was  selected  by  me  as  typical.  In  the  specimens  cor- 
puscles in  many  different  stages  of  development  are  found  together  and  the  se- 
lection of  a  typical  corpuscle  is  difficult.  The  choice  is  necessarily  somewhat 
arbitrary.  The  drawings  illustrate  the  progress  of  development  correctly,  except 
that  the  transition  from  the  last  nucleated  stage.  No.  6,  to  the  final  cup-shaped 
stage,  No.  8,  is  still  subject  to  discussion,  but  No.  7  was  drawn  from  an  actual 
corpuscle,  which  had  certainly  lost  its  nucleus  and  become  smaller,  and  apparently 
was  just  beginning  to  assume  the  cup-shape.  How  the  nucleus  disappears  is  not 
known  with  certainty;  there  are  two  principal  views,  the  first  that  the  nucleus 
is  extruded,  the  second  that  it  is  dissolved  by  the  rest  of  the  cell.  The  problem 
of  the  disappearance  of  the  nucleus,  though  very  important  cytologically,  is  of 
secondary  interest  for  the  main  purpose  of  the  present  lecture. 

^  For  example,  F.  M.  Balfour,  Works,  vol.  i.,  p.  50. 


78 


AGE,  GROWTH,  AND  DEATH 


Its   maximum,    No.    3,    and    the   corpuscle   is   in  the 
Ichthyopsidan  stage, ^  which   means  the  stage   which 


Fig.  25.     Life  History  of  Blood  Corpuscles,  Rabbit  Embryos. 

No.  I.  Embryo  of  8  days,  6  hours,  No.  8S3.  No.  2.  Embryo  of  9  days. 
No.  621.  No.  3,  Embryo  of  9  days,  12  hours.  No.  567.  No.  4.  Embryo  of 
10  days,  No.  940.  No.  5.  Embryo  of  ir  days.  No.  556.  No.  6.  Embryo  of 
14  days,  18  hours.  No.  143.  No.  7.  Embryo  of  16  days,  12  hours,  No.  1229. 
No.  8.     Embryo  of  18  days,  No.   167. 

is  permanent  and  the  highest  attained  in  fishes  and 
amphibians.  The  next  stage.  No.  4,  is  characterised 
by  a  shrinkage  of  the  nucleus,  a  degenerative  change, 
but  bringing  the  physiological  advantage  of  more 
room  for  haemoglobin  in  the  corpuscles.  When  the 
nucleus  shrinks  it  loses  the  granular  appearance  it 
had  before  and  also  stains  more  deeply  with  the  mi- 
croscopists'  dyes,  Nos.  5  and  6.  This  is  called  the 
Sauropsidan  stage,  ^  because  it  is  that  which  is  per- 
manent and  the  highest  attained  in  reptiles  and  birds. 


*  C.  S.  Minot,  "  Morphology  of  the  Blood  Corpuscles,"  Proc.  Amer.  Assoc, 
Adv.  Science,  xxxix.  (1890),  p.  341,  and  Anatomise ker  Anzeiger,  v.,  p.  601. 


THE  CELLULAR  CHANGES  OF  AGE  79 

Next  the  nucleus  disappears,  No.  7,  probably  by  being 
completely  expelledt  from  the  cell,  and  by  further  con- 
traction the  enucleate  cell  assumes  the  cup-shape, 
thus  evolving  the  true  mammalian  non-nucleated  red 
corpuscle,  No.  8.  The  cells  have  been  differentiated 
and  are  now  degenerating.  The  last  stage  of  all  is 
their  death  and  removal.^  Their  usual  end  is  break- 
ing up  into  small  fragments,  which  are  then  eaten  by 
phagocytes  and  so  disposed  of.  Sometimes,  however, 
corpuscles  are  devoured  whole  by  phagocytes.  It  is 
possible  that  corpuscles  are  normally  destroyed  by 
imbibing  fluid  until  they  burst,  as  is  said  to  occur 
under  pathological  conditions.  To  recapitulate:  i,  the 
cells  have  little  protoplasm  ;  2,  the  protoplasm  grows ; 
3,  differentiation  occurs ;  4,  degeneration;  5,  disinte- 
gration of  the  cells  ;  6,  removal  of  their  remains. 

Let  us  turn  from  the  study  of  details  and  illustra- 
tions, to  the  examination  of  general  considerations. 
Our  first  endeavour  must  be  to  answer  the  question  : 
How,  from  the  standpoint  of  cytomorphosis,  ought  we 
to  look  upon  old  age  ?  Cytomorphosis,  the  succes- 
sion of  cellular  changes  which  goes  on  in  the  body,  is 
always  progressive.  It  begins  with  the  earliest  de- 
velopment, continues  through  youth,  is  still  perpetu- 
ally occurring  at  maturity  and  in  old  age.  The  r6le  of 
the  last  stage  of  cytomorphosis,  that  is,  of  death  in  life, 
is  very  important,  and  its  importance  has  only  lately 
become  clear  to  us.  I  doubt  very  much  if  the  con- 
ception is  at  all  familiar  to  the  members  of  this  audi- 

'  Compare  Weidenreich,  Anaiotn.  Anzeiger,  xxiv.,  pp.  186-192. 


8o  AGE,  GROWTH,  AND  DEATH 

ence.  Nevertheless  the  constant  death  of  cells  is  one 
of  the  essential  factors  of  development,  and  much  of 
the  progress  which  our  bodies  have  made  during  the 
years  we  have  lived  has  been  conditional  upon  the 
death  of  cells.  As  we  have  seen,  cytomorphosis, 
when  it  goes  through  to  the  end,  involves  not  only  the 
differentiation  but  the  degeneration  and  death  of  the 
parts.  There  are  many  illustrations  of  this  which  I 
might  cite  to  you  as  examples  of  the  great  importance 
of  the  destruction  of  parts.  Thus  there  is  in  the  em- 
bryo before  any  spinal  column  is  formed  an  easily 
visible  structural  axis  which  is  termed  the  notochord. 
In  the  young  mammalian  embryo  this  structure  is 
clearly  present  and  plays  an  important  part,  but  in  the 
adult  it  has  almost  disappeared,  and  its  disappearance 
begins  very  early  during  embryonic  life.  There  are 
numerous  blood-vessels  which  we  find  to  occur  in  the 
embyro,  both  those  which  carry  the  blood  away  from 
the  heart  and  those  which  bring  blood  to  the  heart, 
which  during  the  progress  of  development  are  entirely 
destroyed,  and  disappear  for  ever.  Knowledge  of  these 
is  to  the  practical  anatomist  and  surgeon  often  of 
great  importance.  Vast  numbers  of  the  smaller  blood- 
vessels which  we  know  commonly  by  the  name  of 
capillaries  exist  only  for  a  time  and  are  then  destroyed. 
There  is  in  the  young  frog,  while  he  is  in  the  tadpole 
stage,  a  kidney-like  organ,  which  on  account  of  its 
position  is  called  the  head-kidney,  but  it  exists  only 
during  the  young  stage  of  the  tadpole.  There  is  later 
produced  another  kidney  which,  from  its  position,  is 


THE  CELLULAR  CHANGES  OF  AGE  8i 

called  the  middle-kidney,  and  which  is  the  only  renal 
organ  found  in  the  adult,  for  the  head-kidney  disap- 
pears in  these  animals  long  before  the  adult  condition 
is  reached.  In  the  mammal  there  is  yet  a  third  kidney. 
We  have  during  the  embryonic  stage  of  the  mammal 
always  a  well-developed  excretory  organ  which  cor- 
responds to  the  middle  or  permanent  kidney  of  the 
frog,  yet  during  embryonic  life  the  greater  part  of  this 
temporary  structure  is  entirely  destroyed.  It  is  dis- 
solved away  and  vanishes,  leaving  only  a  few  remnants 
of  comparatively  little  importance  in  the  adult.  The 
new  structure,  the  permanent  kidney  which  we  have, 
takes  its  place  functionally.  Large  portions  of  the 
tissues  which  arise  in  the  embryo  are  destroyed  at 
the  time  of  birth,  and  take  no  share  in  the  subsequent 
development  of  the  child.^  If  we  follow  out  with 
the  microscope  the  various  changes  which  go  on  in 
the  developing  body  we  see  revealed  to  us  a  very 
large  number  of  cases  of  death  of  tissues,  followed  by 
their  removal.  Thus  the  cartilage  which  exists  in  the 
early  stages  dies  and  is  dissolved  away,  and  its  place 
is  taken  by  bone.  Many  of  the  bony  elements  of  the 
skeleton  in  the  adult,  in  the  embryo  exist  merely  as 
cartilage,  yet  the  cartilage  is  not  converted  into  bone 
but  is  destroyed  and  part  passu  its  place  taken  by 
bone.2     There   is  overlying  the  heart  of  a  child  at 

'  Reference  is  made  to  the  after-birth,  which  includes  the  structures  known 
anatomically  as  the  umbilical  cord,  the  amnion  (the  "caul"  of  the  midwife),  the 
chorion  Iteve,  and  the  fetal  placenta. 

^  The  conversion  of  cartilage  into  bone  was  studied  by  many  investigators 
especially  between  1845  and  1870,  and  was  the  subject  of  prolonged  and  ani- 
6 


82  AGE,  GROWTH,  AND  DEATH 

birth  a  well-developed  gland  known  as  the  thymus. 
After  childhood  this  undergoes  a  retrograde  develop- 
ment ;  it  becomes  gradually  absorbed  and  persists  only 
in  a  rudimentary  condition.  With  the  loss  of  the  teeth 
occurring  during  infancy,  you  are  familiar,  and  know 
that  the  first  set  of  teeth  are  but  for  a  short  period, 
and  are  to  be  replaced  by  the  permanent  set.  In  very 
old  persons  we  see  a  great  deal  of  the  bony  material 
absorbed,  and  this  absorption  of  the  bone  is  a  phe- 
nomenon which  occurs  at  almost  every  period  of  the 
development.  Portions  of  the  epidermis  or  outer  skin 
are  constantly  shed,  as  is  well  known,  and  the  loss  of 
hair  and  the  loss  of  portions  of  our  nails  are  so  famil- 
iar to  us  that  we  hardly  heed  them.  Of  the  constant 
destruction  of  the  cells  which  are  found  in  the  lining 
of  the  intestine,  I  have  already  spoken.  At  all  times 
in  the  body  there  is  a  vast  amount  of  destruction  of 
blood  corpuscles  going  on,  a  destruction  which  is  phys- 
iologically indispensable,  for  the  material  which  the 
blood  corpuscles  furnish  is  used  in  many  ways.  For 
instance,  the  pigment  which  occurs  in  the  hair  is  sup- 
posed to  be  derived  from  the  chemical  substances  the 
use  of  which  the  body  obtains  by  destroying  blood 

mated  debates,  one  might  almost  say  of  constant  controversy.  This  need  not 
be  wondered  at  for  the  changes  involved  are  very  complicated,  owing  to  the 
fact  that  the  formation  and  destruction  of  cartilage,  the  formation  of  new  and 
the  removal  of  old  bone,  and  the  development  of  a  new  tissue  (marrow)  all  go 
along  together,  and  often  may  all  be  seen  at  once,  each  in  various  phases,  within 
the  limits  of  a  single  microscopic  field  of  view.  Our  present  knowledge  renders 
it  certain  that  the  cartilage  degenerates,  dies,  and  disappears  and  takes  no 
share  in  the  production  of  bone.  That  certain  rare  exceptions  to  this  rule  occur 
has  been  maintained,  but  the  evidence  is,  in  my  opinion,  unconvincing. 


THE  CELLULAR  CHANGES  OF  AGE  ^^^ 

corpuscles.  One  of  the  most  familiar  instances  of  des- 
truction is  that  of  the  tail  of  the  tadpole.  The  young 
frog  and  the  young  toad  durmg  their  larval  stages  live 
in  the  water  and  each  of  them  is  furnished  with  a  nice 
tail  for  swimming  purposes.  As  the  time  approaches 
for  the  metamorphosis  of  the  tadpole  Into  the  adult,  the 
tail  is  gradually  dissolved  away.  It  is  not  cast  off,  but 
it  is  literally  dissolved,  resorbed,  and  vanishes  ulti- 
mately altogether. 

^  It  is  evident  that  such  a  vast  amount  of  destruc- 
tion of  living  cells  could  not  be  maintained  in  the 
body  without  the  body  going  entirely  to  destruction 
itself,  were  there  not  some  device  for  making  good 
the  losses  which  are  thus  brought  about.     We  find 
in  fact  that  there  is  always  a  reserve  of  cells  kept  to 
make  good  the  loss  which  it  is  essential  should  be 
made  good.     Some  losses  apparently   do   not  have 
to  be  repaired,   but   the  majority  of  them  must  be 
compensated  for,  and  this  is  done  by  having  in  the 
body  a  reserve  supply  of  cells  which  can  produce  new 
cells  of  the  sort  required.    This  leads  us  to  considera- 
tion of  the  phenomenon  of  regeneration  and  of  the 
repair  of   parts.     These   phenomena  we    can    better 
take  up  later  in  our  course,  after  we  shall  have  dealt 
with    the    general    processes    of    development    and 
growth.      From  the  study  of  regeneration  we  shall  be 
able  to  confirm  the  explanation  of  old  age,  which  I  want 
to  lay  before  you.      This  confirmation  is  so  important 
that  it  will  be  better  taken  up  in  a  separate  lecture, 
than  slipped  in  now  when  the  hour  is  nearly  by. 


84  '      AGE,  GROWTH,  AND  DEATH 

Old  age,  after  what  I  have  said,  I  think  you  will 
all  recognise  as  merely  the  advanced  and  final  stage 
of  cytomorphosis.  Old  age  differs  but  little  in  its 
cytomorphosis  from  maturity ;  maturity  differs  much 
from  infancy  ;  infancy  differs  very  much  indeed  from 
the  embryo  ;  but  the  embryo  differs  enormously  from 
the  germ  in  its  cytomorphic  constitution.  We  know 
that  in  the  early  time  comes  the  great  change,  and 
this  fact  we  shall  apply  for  purposes  of  interpretation 
later  on.  Cytomorphosis  is  then  a  fundamental  no- 
tion. It  gives  us  in  a  general  law,  a  comprehensive 
statement  of  all  the  changes  which  occur  in  the  body. 
None,  in  fact,  are  produced  at  any  period  in  any 
of  us  except  in  accordance  with  this  general  cyto- 
morphic law.  There  is,  first,  the  undifferentiated 
stage,  then  the  progressive  differentiation  ;  next  there 
follows  the  degenerative  change  ending  in  death,  and 
last  of  all,  the  removal  of  the  dead  cells.  Such  we 
may  conveniently  designate  as  the  four  essential 
stages  of  cytomorphosis.  This  cytomorphosis  is  at 
first  very  rapid  ;  afterwards  it  becomes  slower.  That 
is  a  significant  thing.  The  young  change  fast ;  the 
old  change  slowly.  We  shall  be  able,  when  we  get  a 
little  farther  along  in  our  study,  to  see  that  in  differ- 
entiation lies  the  explanation  of  a  great  many  of  the 
known  phenomena  of  biology,  lies  the  explanation  of 
our  conception  of  cell  structures ;  and  in  it  also  lies 
not  only  the  explanation  of  the  death  of  cells,  but 
also,  as  it  seems  to  me — and  this  is  one  of  the  points 
that  I  shall  want  particularly  to  bring  forward  before 


THE  CELLULAR  CHANGES  OF  AGE  85 

the  close  of  the  course, — of  general  death,  that  which 
we  mean  by  death  in  common  parlance,  when  the 
continuation  of  the  life  of  the  individual  ceases,  and 
is  thereafter  bodily  impossible.  The  explanation  of 
death  is  one  of  the  points  at  which  we  shall  be  aiming 
in  the  subsequent  lectures  of  the  course. 

Now  we  know  that  in  connection  with  age  there 
is  always  growth.  I  propose,  therefore,  in  the  next 
lecture  to  take  up  the  subject  of  growth.  We  shall 
arrive  at  some  paradoxical  conclusions,  for  it  can 
be  shown  by  merely  statistical  reckonings  that  our 
notion  that  man  passes  through  a  period  of  devel- 
opment and  a  period  of  decline  is  misleading,  in 
that  in  reality  we  begin  with  a  period  of  extremely 
rapid  decline,  and  then  end  life  with  a  decline  which 
is  very  slow  and  very  slight.  The  period  of  most 
rapid  decline  is  youth  ;  the  period  of  slowest  decline 
is  old  age,  and  that  this  statement  is  correct  I  shall 
hope  to  prove  to  you  with  the  aid  of  tables  and 
lantern  illustrations  at  the  next  lecture. 


Ill 


THE    RATE    OF    GROWTH 


L 


A  DIES  AND  GENTLEMEN:  In  the  first  of 
the  lectures,  I  described  those  grosser  character- 
istics of  old  age,  which  we  ourselves  can  readily  dis- 
tinguish, or  which  an  anatomical  study  of  the  body 
reveals  to  us.  In  the  second  lecture  I  spoke  of  the 
microscopic  alterations  which  occur  in  the  body  as 
it  changes  from  youth  to  old  age.  But  besides  the 
changes  which  we  have  already  reviewed,  there  are 
those  others,  very  conspicuous  and  somewhat  known 
to  us  all,  which  we  gather  together  under  the  com- 
prehensive term  of  growth.  It  is  growth  which  I 
shall  ask  you  to  study  with  me  this  evening,  and  I 
shall  hope,  by  the  aid  of  our  study,  to  reinforce  in 
your  minds  the  conclusion  which  I  have  already 
indicated,  that  the  early  period  of  life  is  a  period  of 
rapid  decline,  and  that  the  late  period  of  life  is  one 
of  slow  decline. 

In  order  to  study  growth  accurately,  it  is  desirable, 
of  course,  to  measure  it,  but  since  we  are  concerned 
with  the  general  problem  of  growth,  we  wish  no  par- 
tial measure,  such  as  that  of  the  height  alone  would 

86 


THE  RATE  OF  GROWTH  87 

be.  And  indeed,  if  we  take  any  such  partial  measure, 
how  could  we  compare  different  forms  with  one  an- 
other? The  height  of  a  horse  is  not  comparable  to 
that  of  a  man  ;  the  height  of  a  caterpillar  is  not 
comparable  to  that  of  any  vertebrate.  Naturally, 
therefore,  we  take  to  measuring  the  weight,  which 
represents  the  total  mass  of  the  living  body,  and  en- 
ables us  at  least  with  some  degree  of  accuracy  to 
compare  animals  of  different  sorts  with  one  another. 
Now  in  studying  this  question  of  the  increase  of 
weight  in  animals,  as  their  age  increases,  it  is  obvi- 
ously desirable  to  eliminate  from  our  experiments  all 
disturbing  factors  which  might  affect  the  rate  of 
growth  or  cause  it  to  assume  irregularities  which  are 
not  mherent  either  in  the  organisation  of  the  animal 
or  in  the  changes  age  produces.  The  animals  which 
belong  to  the  vertebrate  sub-kingdom,  of  which  we 
ourselves  are  members,  can  be  grouped  in  two  large 
divisions  according  to  the  natural  temperature  of 
their  bodies.  The  lower  vertebrates,  the  fishes, 
frogs,  and  their  kin,  are  animals  which  depend  for 
their  body  temperature  more  or  less  on  the  medium 
in  which  they  live.  The  other  division  of  vertebrate 
animals,  which  includes  all  the  higher  forms,  are  so 
organised  that  they  have  within  certain  limits  the 
power  of  regulating  their  own  body  temperature. 
Now  it  is  easily  to  be  observed — and  any  one  who 
has  made  observations  upon  the  growth  of  animals 
can  confirm  this — that  animals  otherwise  alike  will 
grow  at  different  speeds  at  different  temperatures. 


88  AGE,  GROWTH,  AND  DEATH 

There  are  animals,  like  the  frogs  and  salamanders, 
which  will  live  at  a  very  considerable  range  of  tem- 
perature and  thrive,  apparently.  No  ultimate  injury 
is  done  to  them  by  a  change  of  their  bodily  tempera- 


FiG.  26.  Four  Tadpoles  of  the  European 
Frog  A'ana  fiisca.  After  Oskar  Hertwig.  The 
four  animals  are  all  of  the  same  age  (three  days)  and 
raised  from  the  same  batch  of  eggs,  but  have  been 
kept  at  different  temperatures. 

A  at  IT. 5°  centigrade.       j5  at  15.0°  centigrade 

C  "  20.0°  "  -Z?  "  24.0°  " 

ture.  Here  we  have  four  young  tadpoles,  (Fig.  26), 
all  of  which  are  exactly  three  days  old.  The  first  of 
these  has  been  kept  at  a  temperature  not  much  above 
freezing;  the  fourth  at  a  temperature  of  about  twenty- 


THE  RATE  OF  GROWTH  89 

four  degrees  centigrade  ;  the  other  two  at  temperatures 
between.  They  are  all  descendants  from  the  same 
batch  of  frogs'  eggs,  and  you  can  see  readily  that  the 
first  one  is  still  essentially  nothing  but  an  ^gg.  The 
second  one,  which  has  had  a  little  higher  temperature, 
already  shows  some  traces  of  organisation,  and  those 
familiar  with  the  development  of  these  animals  can 
see  in  the  markings  upon  the  surface  the  first  indica- 
tions of  the  differentiation  of  the  nervous  system. 
The  third  has  been  kept  at  a  considerably  warmer 
temperature,  and  is  now  obviously  a  young  tadpole  ; 
here  are  the  eyes,  the  rudimentary  gills,  the  tail,  etc. 
While  the  fourth  tadpole,  which  was  maintained  at 
the  best  temperature  for  the  growth  of  these  animals, 
has  advanced  enormously  in  its  development.  Ob- 
viously, should  we  make  experiments  upon  animals 
of  this  class  it  would  be  necessary  to  keep  them  at  a 
uniform  temperature,  if  we  wished  to  study  their  rate 
of  development,  and  that  is,  for  very  practical  rea- 
sons, extremely  difficult  and  unsatisfactory.  Far  bet- 
ter it  has  seemed  for  our  study  of  growth  to  turn 
to  those  animals  which  regulate  their  own  tempera- 
ture. This,  accordingly,  I  have  done,  and  the  animal 
chosen  for  these  studies  was  the  guinea-pig,  a  crea- 
ture which  offers  for  such  investigations  certain  de- 
finite advantages.  It  is  easily  kept ;  it  is  apt  to 
remain,  with  proper  care,  in  good  health.  Its  food 
is  obtainable  at  all  seasons  of  the  year,  in  great 
abundance,  and  at  small  expense.  The  animals  them- 
selves being  of  moderate  size  do  not,  of  course,  re- 


90  AGE,  GROWTH,  AND  DEATH 

quire  such  extraordinary  amounts  of  food  as  the 
large  animals,  should  we  experiment  with  them.  Ac- 
cordingly with  guinea-pigs  I  began  making,  years 
ago,  a  long  series  of  records,  taking  from  day  to  day, 
later  from  week  to  week,  and  then,  as  the  animals 
grew  older,  month  by  month,  the  weight  of  recorded 
individuals.  There  was  thus  obtained  a  body  of 
statistics  which  rendered  it  possible  to  form  some 
idea  of  the  rapidity  of  growth  of  this  species  of 
mammal. 

Now  in  regard  to  the  rapidity  of  growth,  it  is  en- 
cessary  that  we  form  clearer  notions  than  perhaps  you 
started  out  with  when  you  came  into  the  hall  this 
evening.  I  will  ask  for  the  next  of  our  pictures  on 
the  screen,  where  we  shall  see  illustrated  to  us  older 
methods  of  recording  the  progressive  growth  of 
animals.  Fig.  27  is  a  chart  taken  from  the  records 
of  my  friend,  Dr.  Henry  P.  Bowditch,  showing  the 
growth  of  school  children  in  Boston.  Here  we  have, 
in  the  lower  part  of  the  figure,  the  two  curves  of 
growth  in  weight.  The  upper  curve  is  the  weight  of 
boys.  We  can  follow  it  back  through  the  succession 
of  years  down  to  the  age  of  five  and  one  half  years, 
when  the  records  begin.  The  child  weighs,  as  you 
see,  a  little  under  forty  pounds  at  that  time.  When 
the  boy  reaches  the  age  of  eighteen  and  one  half 
years,  he  approaches  the  adult  size,  and  weighs  well 
over  130  pounds.  Here  then  we  see  growth  repre- 
sented to  us  in  the  old  way,  the  progressive  increase 
of  the  animal  as  it  goes  along  through  the  succession 


THE  RATE  OF  GROWTH 


91 


of  years.  Now  this  is  a  way  which  records  the  actual 
facts  satisfactorily.  It  shows  the  progressive  changes 
of  weight  as  they  really  occur  ;  but  it  does  not  give 


im,. 

64 

62 
60 
58 
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52 
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Fig.  27.     Curves  Showing  the  Growth  of  Boston  School  Children 
IN  Height  and  Weight. —  After  H.  P.  Bowditch. 

US  a  correct  impression  of  the  rate  of  growth.  Con- 
cerning the  rate  of  growth,  some  more  definite  notion 
must  be  established  in  our  minds  before  we  can  be 
said  to  have  an  adequate  conception  of  the  meaning 
of  that  term.^      It  is  from  the  study  of  the  statistics 

'  The  method  described  in  the  text  of  determining  the  rate  of  growth  was 


92  AGE,  GROWTH,  AND  DEATH 

of  the  guinea-pigs,  and  of  other  animals  which  I 
have  since  had  an  opportunity  of  experimenting  with, 
that  we  get  indeed  a  clearer  insight  as  to  what  the 
rate  of  growth  really  is  and  really  means. 

I  should  like  to  pause  a  moment  to  say  that  when 
I  first  published  a  paper  upon  the  subject  of  growth, 
it,  fortunately  for  me,  interested  the  late  Dr.  Benja- 
min A.  Gould.  The  experiments  which  I  had  made 
and  recorded  in  that  first  publication  came  to  a  sud- 
den end,  owing  to  a  disaster  for  which  I  myself  was 
personally  not  responsible,  by  which  practically  my 
entire  stock  of  animals  was  suddenly  destroyed.  Dr. 
Gould,  after  consulting  with  me,  proposed  that  I 
should  have  further  aid  from  the  National  Academy 
of  Sciences,  and  through  his  intervention  I  obtained 
a  grant  from  the  Bache  fund  of  the  Academy.  That 
liberal  grant  enabled  me  to  continue  these  researches, 
and  this  is  the  first  comprehensive  presentation  of 
my  results  which  I  have  attempted.  In  this  and  the 
subsequent  lectures,  I  hope  that  enough  of  what  is 
new  in  scientific  conclusions  may  appear  to  make 
those  to  whose  generosity  I  am  indebted  feel  that  it 
has  been  worthily  applied.  I  cannot  let  such  an  oc. 
casion  as  this  pass  by  without  expressing  publicly  my 
gratitude  to  Dr.  Gould  for  his  encouragement  and 
support  at  a  time  when  I  most  keenly  appreciated  it. 

If  animals  grow,  that  which  grows  is  of  course  the 
actual  substance  of  the  animal.      Now  we  might  say 

first  defined  and  advocated  by  me  in  my  article,  "  Senescence  and  Rejuvena- 
tion,"^(pMrw.  of  Physiol.,  vol.  xii.,  pp.  97-153  (1891). 


THE  RATE  OF  GROWTH 


93 


that  given  so  much  substance  there  should  be  equal 
speed  of  growth,  and  we  should  expect,  possibly,  to 
find  that  the  speed  would  be  more  or  less  constant. 
I  can  perhaps  illustrate  my  meaning  more  clearly, 
and  briefly  render  it  distinct  in  your  minds,  by  saying 
that  if  the  rate  of  growth,  as  I  conceive  it,  should  re- 
main constant,  it  would  take  an  animal  at  every  age 
just  the  same  length  of  time  to  add  ten  per  cent,  to 
its  weight ;  it  would  not  be  a  question  whether  a  baby 
grew  an  ounce  in  a  certain  length  of  time,  and  a  boy 
a  pound  in  the  same  time,  for  the  pound  might  not  be 
the  same  percentage  of  advance  to  the  boy  that  the 
ounce  would  be  to  the  baby.  In  reality  with  an  ad- 
vance of  an  ounce  the  baby  might  be  growing  faster 
than  the  older  boy  with  the  addition  of  the  pound. 

To  determine  the  rate  I  devised  the  following 
method.^  Take  the  weight  at  a  given  age,  and  the 
weight  at  the  next  older  age  for  which  there  are 
observations.  From  these  data  calculate  the  average 
daily  increase  in  v/eight  for  the  period  between  the 
two  determinations  of  the  weight,  then  express  the 
daily  increase  as  a  percentage  of  the  weight  at 
the  beginning  of  the  period.  From  a  series  of  de- 
terminations the  daily  percentage  increments  are 
readily  calculated  for  successive  ages.  Subsequently 
the  method  was  modified  for  the  study  of  the  rate  of 
growth  in  man  by  substituting  the  monthly,  or  even 
yearly,  percentage  increments  for  the  daily.  This 
method  is  not  mathematically  exact,  since  the  grow- 


94 


AGE,  GROWTH,  AND  DEATH 


ine  weight  is  a  variable  function  of  the  aoe,  but  it  is 
sufficiently  exact  for  our  present  needs,  and  has  the 
advantages  of  simplicity  and  rapidity  in  its  practical 
application. 

In  the  next  slide  (Fig.  28)  which  we  are  to  see 
upon  the  screen  we  have  my  method  of  measuring  the 
rate  of  growth  illustrated  graphically.  There  is  here 
a  curve  which  represents  the  rate  of  growth  of  male 
guinea-pigs.  The  figures  at  the  bottom  indicate  the 
age  of  the  animals  in  days.  When  guinea-pigs  are 
born  they  are  very  far  advanced  in  development,  and 
the  act  of  birth  seems  to  be  a  physiological   shock 


Pe^ice/Tviayae.  JruybE/nie/n^.    iTlale^. 


a  5811    n    23   29  35  38  45  60  75  90  105  120  135  ISO  165 


UOday^ 


Fig.  28.    Curve  Showing  the  Daily  Percentage  Increments  in  Weight 
OF  Male  Guinea-pigs. 


from  which  the  organism  suffers,  and  there  is  a  lessen- 
ing of  the  power  of  growth  immediately  after  birth. 
But   in    two   or   three   days   the   young   are   fully  re- 


THE  RATE  OF  GROWTH  95 

covered,  and  after  that  restoration  they  can  add  over 
five  per  cent,  to  their  weight  in  a  single  day.  But  by 
the  time  they  are  17  days  old,  as  represented  by  this 
line,  they  can  add  only  four  per  cent,  and  by  the  time 
they  are  24  days  old,  less  than  two  per  cent;  at  45 
barely  over  one  per  cent;  at  70  still  over  one  per 
cent;  at  90  less;  at  160  less;  and  towards  the  end 
the  curve  continues  dropping  off,  coming  gradually 
nearer  and  nearer  to  zero,  to  which  it  closely  ap- 
proximates at  the  age  of  240  days.  In  about  a  year, 
the  guinea-pig  attains  nearly  its  full  size.  You  notice 
that  this  curve  is  somewhat  irregular.  Such  is  very 
apt  to  be  the  result  from  statistics  when  the  number 
of  observations  is  not  very  large.  It  means  simply 
that  there  was  not  a  sufficiently  large  number  of 
animals  measured  to  give  an  absolutely  even  and 
regular  set  of  averages.  But  the  general  course  of 
the  curve  is  very  instructive.  In  the  earlier  condition 
of  the  young  guinea-pig  there  is  a  rapid  decline ;  in 
the  later,  a  slow  decline.  The  change  from  rapid  to 
slow  decline  is  not  sudden,  but  gradual,  as  you  see 
by  the  general  character  of  this  curve. 

In  the  next  slide  (Fig.  29)  we  can  see  immediately 
that  what  I  have  asserted  as  true  of  the  male  is  equally 
true  of  the  female,  althouorh  the  values  which  we  have 
differ  slightly  in  the  two  sexes,  and  there  are  accidental 
but  not  significant  variations  in  this  curve  as  in  the 
first.  Here  also  we  observe  at  once  an  early  period  of 
rapid  decline  in  which  the  rate  of  growth  is  going 
down  and  down — a  period  of  slight  decline  in  which, 


96 


AGE,  GROWTH,  AND  DEATH 


to  be  sure,  it  is  going  down  still,  but  with  diminished 
rapidity. 

There  is  another  method  by  which  we  can  represent 


Pe/UjemjtcL^  Joa/yie/me/n^.    J'^rrui/e<) 


2  5811    n    23    29   3S3e    +5 


60  75  90  105  IZO  135  ISO  165  ISO  I9S  2IOi:^a^ 


Fig.  29.    Curve  Showing  the  Daily  Percentage  Increments  in  Weight 
OF  Female  Guinea-pigs. 

this  change  in  the  rate  of  growth  which  will  perhaps 
help  to  illustrate  it ;  and  in  the  next  of  our  pictures 
(Fig.  30)  we  see  this  other  form  of  representation. 
The  first  vertical  line  represents  the  length  of  time 
which  it  takes  a  young  male  guinea-pig  to  add  ten  per 
cent,  to  its  weight  the  first  time.  Here  the  third 
time — the  fourth — the  fifth — and  you  see  as  it  is 
growing  older  and  older  it  takes  the  animal  longer 
and  longer  to  add  ten  per  cent,  to  its  weight.  Finally 
we  get  to  the  nineteenth  addition,  and  we  see  that 
the  period  is  very  long  indeed.  How  long  that 
period  is  we  can  judge  by  the  figures  upon  the  left, 
which  represent  the  length  of  the  periods  in  days. 


THE  RATE  OF  GROWTH 


97 


From  the  base  line  to  the  one  marked  "ten  "  is  a  pe- 
riod of  ten  days,  and  you  see  that  the  guinea-pig  in 
adding  to  its  weight  ten  per  cent,  for  the  nineteenth 
time  does  it  so  slowly  that  it  requires  ten  days  and 
more ;  for  the  twenty-first  time,  nearly  twenty ;  for 


50 


Xem^o^  o^  W%  -PeA^cod^.    7/ki^ 


40 


30 


20 


10 


i^eAlod.'i    4^    5    6     7    8    9    10    II    12    13   14   15   16   17   18   19  20  21   ZZ  23  24  25 


Fig.  30.     Curve  Showing  the  Length  of  Time  Required  to  Make  Each 
Successive  Increase  of  id  per  cent,  in  Weight  by  Male  Guinea-pigs. 

the  twenty-second  time,  nearly  forty  days.  At  last 
the  number  of  observations  becomes  small,  and  the 
curve  grows  irregular.  Thus  we  demonstrate  that  as 
the  animal  grows  older  it  takes  longer  and  longer  to 
add  ten  per  cent,  to  its  weight.  In  the  other  sex,  as 
the  next  slide  shows,  (Fig,  31),  the  same  phenomena 
can  be  clearly  demonstrated  ;  here  are  the  periods  as 


AGE,  GROWTH,  ANU  DEATH 


before,  lengthening  out,  as  you  see,  at  first ;  then  be- 
coming very  long  indeed.  In  the  following  slide  I 
have  another  form  of  representation  of  this  same  phe- 


70 


JC^m^atA  oi  W%  p€A.covU    3'€mta£&^. 


60 


50 


40 


30 


20 


J>eA-^<rd.Z   4    5    6     7    8    9    10   II    12   13    14  15    16    l7   18    19  20  21  22  23  24  25 


Fig.  31.    Curve  Showing  the  Length  of  Time  Required  to  Make  Each 
Successive  Increase  of  10  per  cent,  in  Weight  by  Female  Guinea-pigs. 

nomenon  as  it  occurs  in  the  human  subject.  Here  is 
a  diagram  of  growth,  (Fig.  32),  which  represents,  as 
accurately  as  I  could  determine  it,  the  curve  complete 
for  man   from   birth   up   to  the  age   of   forty   years. 


THE  RATE  OF  GROWTH 


99 


It  has  been  calculated  by  a  simple  mathematical  pro- 
cess where  these  ten-per-cent.  increments  fall,  and 
from  each  point  in  this  curve  where  there  has  been 
such  an  increment,  a  vertical  line  has  been  drawn,  as 
you  see  here.  These  lines  are  very  close  together  at 
the  start.  One  ten  per  cent,  after  another  follows  in 
a  short  interval  of  time,  but  gradually  the  time,  as 


as^yrs             30^rs               ^^yrs 

30              i2S.02lbS. 

A 

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12  yr^ 
-25-           77  62  lbs                           / 

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60 

20               48.20  lbs. 

y 

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40 

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0 

Fig.  32.  Curve  Showing  the  Growth  of  Man  from  Birth  to  Ma- 
turity, with  vertical  lines  added  to  mark  the  duration  of  the  periods  for  each 
ID  per  cent,  addition  to  the  weight. 

indicated  by  the  space  between  two  of  these  vertical 
lines,  increases,  and  when  the  individual  is  three  years 
old,  you  can  see  there  has  been  a  very  great  lengthen- 
ing out  of  the  period  which  is  necessary  for  it  to  add 


loo  AGE,  GROWTH,  AND  DEATH 

ten  per  cent,  to  its  weight.  Then  it  comes  at  the 
age  of  twelve  to  a  period  of  slightly  more  rapid 
growth,  a  fluctuation  which  is  characteristic  of  man, 
but  does  not  appear  in  the  majority  of  animals.  After 
that  comes  very  rapidly  the  enormous  lengthening  of 
the  period.  I  have  not  added  the  last  ten  per  cent, 
because  the  curve  here  at  the  top,  you  see,  is  not 
very  regular,  and  it  could  not  be  calculated  with  cer. 
tainty.  Our  diagram  is  merely  another  form  of 
graphic  representation  of  the  fact  that  the  older  we 
are  the  longer  it  takes  us  to  grow  a  definite  propor- 
tional amount. 

Figure  33  carries  us  into  another  part  of  our 
study,  away  from  the  mammals  which  we  have  thus 
far  considered,  into  the  class  of  birds.  The  growth 
of  chickens  is  represented  here.  Now  a  chicken  is 
born  in  a  less  matured  state  than  a  guinea-pig,  and 
has  a  good  deal  higher  efficiency  of  growth  at  first* 
In  a  chicken,  as  in  a  guinea-pig,  birth  is  a  disturbing 
factor,  and  growth  immediately  after  the  hatching  of 
the  chicken  is  a  little  impeded,  but  the  chick  quickly 
recovers  and,  as  we  see,  the  first  time  when  the  rate 
can  be  distinctly  measured  we  get  a  nine-per-cent. 
addition  to  the  weight  in  a  single  day.  In  a  chicken, 
as  in  the  guinea-pig,  the  rate  gradually  diminishes. 
The  change  from  the  rapid  decline  at  first  to  the 
later  slower  decline  is  more  gradual ;  the  curve  is 
more  distinctly  marked  in  the  chicken  as  a  round 
curve.  There  is  not  in  the  bird  so  distinct  a  separa- 
tion of  the   preliminary  rapid  decline  and  the   later 


THE  RATE  OF  GROWTH  loi 

slower  decline  as  we  find  in  the  guinea-pig.  The 
curve  again  is  very  irregular  because  I  had  only  a 
very  limited  number  of  observations  upon  the  weight 
of  chicks.^  The  other  sex,  as  the  next  slide  will 
show,  presents  similar  phenomena,  though  the  female 
chickens  do  not  grow  quite  as  fast  as  their  brothers. 
Here  we  notice  an  initial  increase  of  almost,  but  not 
quite,  nine  per  cent,,  which  rapidly  diminishes.      After 


03i8l3l8a283J38  46    55    66     ^^       90        '06 


Fig.  33.    Curve  Showing  the  Daily  Percentage  Increments  in  Weight 
BY  Male  Chickens. 


the  chick  is  two  months  old  it  never  adds  as  much  as 
2,fo  per  diem  to  its  weight.  It  loses  in  the  first  two 
months  from  a  capacity  to  add  nine  per  cent.,  down  to 
a  capacity  of  adding  less  than  three  daily.  It  loses 
in  two  months  two  thirds  of  its  power  of  growth, 
for  from   nine  to  zero  is  divisible  into  two  parts,  of 

'  See  Appendix  No.  II. 


I02 


AGE,  GROWTH,  AND  DEATH 


which  the  first,  from  nine  down  to  three,  would  be 
two  thirds,  and  the  second,  from  three  to  zero,  would 
be  one  third.  Here  then  we  learn  that  two  thirds  of 
the  decline  which  occurs  in  the  life  of  a  chick  takes 


1                                          /hiceovta^  Jiic'ie/m£mfy       CAccA^     J^moAi). 

/ 

41 

\ 

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i. 

/ 

\ 

^ 

N 

\ 

p-^ 

^ 

1 — 

03^8  131822263338  46     56    66 


Fig  34.     Curve  Showing  the  Daily  Percentage  Increments  in  Weight 
BY  Female  Chickens, 

place  in  two  months,  and  for  the  rest  of  the  life  of  the 
bird  there  is  a  decline  of  one  third.  That,  you  must 
acknowledge,  is  an  extraordinary  and  most  impressive 
difference. 

If  it  be  true  that  the  more  rapid  growth  depends 
upon  the  youth  of  the  individual,  — its  small  distance 
in  time  from  its  procreation, — then  we  may  perhaps, 
by  turning  to  other  animals  which  are  born  in  a  more 
immature  state,  get  some  further  insight  into  these 
changes ;  and  that  I  have  attempted  to  do  by  my  ob- 
servations upon  the  development  of  rabbits.'    Rabbits, 

'  See  Appendix  No.  I. 


THE  RATE  OF   GROWTH  103 

as  you  know,  are  born  in  an  exceedingly  immature 
state.  They  are  blind,  they  are  naked,  they  are  al- 
most incapable  of  definite  movements,  quite  incapable 
of  locomotion,  and  are  hardly  more  than  little  imper- 
fect creatures  lying  in  the  nest  and  dependent  utterly 
upon  the  care  of  the  mother,  quite  unable  to  do  any- 
thing for  themselves  except  take  the  milk  which  is 
their  nourishment.  They  are  indeed  animals  born  in 
a  much  less  advanced  stage  than  are  the  guinea-pigs, 
which  appear  clothed  with  hair,  having  open  eyes  and 
sight,  and  able  to  run  about,  although  rather  wobbly 
the  first  day  or  two.  Upon  the  screen  we  see  this 
interesting  result  demonstrated  to  us,  that  a  male 
rabbit,  the  fourth  day  after  its  birth,  is  able  to  add 
over  seventeen  per  cent,  to  its  weight  in  one  day. 
From  that  the  curve  drops  down,  as  you  see,  with 
amazing  rapidity,  so  that  here  at  an  age  of  twenty- 
three  days  the  rabbit  is  no  longer  able  to  add  nearly 
eighteen  per  cent,  daily,  but  only  a  little  over  six.  At 
the  end  of  two  months  from  its  birth,  the  growth 
power  of  the  rabbit  has  dropped  to  less  than  two  per 
cent.,  and  at  two  months  and  a  half  it  has  dropped  to 
one.  The  drop  in  two  and  a  half  months  has  been 
from  nearly  eighteen  per  cent,  down  to  one  per  cent., 
and  the  rest  of  the  loss  of  one  per  cent,  i-s  extended 
over  the  remaining  growing  period  of  the  rabbit. 
Could  we  have  a  more  definite  and  certain  demon- 
stration of  the  fact  that  the  decline  is  most  rapid  in 
the  young,  most  slow  in  the  old  ?  It  is  not  in  this 
case  any  more  than  in  the  others  the  one  sex  that 


1 

Pe^tceyrdaae.  J'yvotje/fne/ni^    JSaMv6) 

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^^^^^-^^^__ 

03  8 

3I8^3^83338       5 

5           7 

7|              10 

64                                     l80aJcz^<^                              -.?7f) 

Fig.  35.    Curve  Showing  the  Daily  Percentage  Increments  in  Weight 
BY  Male  Rabbits. 


104 


iBO  da^ 


03&\3\B2i283iV         55 
38 

Fig.  36.    Curve  Showing  the  Daily  Percentage  Increments  in  Weight 
BY  Female  Rabbits. 


105 


io6  AGE,  GROWTH,  AND  DEATH 

demonstrates  this  fact,  for  in  the  female  we  find 
exactly  the  same  phenomena,  as  the  next  sHde  will 
show.  The  irregularities  are  not  significant.  The 
strange  dip  at  thirty-eight  days,  for  instance,  corres- 
ponds to  an  illness  of  some  of  the  rabbits  which  were 
measured,  but  they  rapidly  recovered  from  it  and 
grew  up  to  be  fine,  nice  rabbits.  If  instead  of  measur- 
ing half  a  dozen  rabbits,  we  had  measured  two 
hundred  or  five  hundred,  these  irregularities  would 
certainly  have  disappeared.  The  females  in  the  case 
of  the  rabbits,  as  in  the  case  of  the  guinea-pigs,  are 
not  able  to  grow  quite  so  fast  at  first.  We  see  here 
sixteen  instead  of  over  seventeen  per  cent,  as  the 
initial  value,  but  the  general  character  of  the  drop  is 
the  same,  enormously  rapid  at  first  and  very  slow 
afterwards.  All  of  our  cases,  then,  show  the  same 
fundamental  phenomena  appearing  with  different 
values. 

Now  in  regard  to  man,  we  do  not  possess  any  such 
adequate  series  of  statistics  of  growth  as  is  desirable. 
We  have  many  records  of  the  weight  of  babies,  by 
which  I  mean  children  from  the  date  of  birth  up  to 
one  year  of  age.  We  have  also  very  numerous  re- 
cords of  school  children,  which  will  extend  perhaps 
from  five  and  one  half  up  to  say  seventeen,  eighteen, 
or  even  nineteen  years.  There  are  records  of  boys 
at  universities,  and  a  still  more  limited  number  of 
weighings  of  girls  at  colleges.  But  all  these  statistics 
piled  together  do  not  give  us  one  comprehensive  set 
of  data  including  all  ages.     This  is  very  much  to  be 


V 


THE  RATE  OF  GROWTH 


107 


regretted,  and  it  would  be  an  Important  addition  to 
our  scientific  knowledge  could  statistics  of  the  growth 
of  man  be  gathered  with  due  precautions.  It  would 
fill  one  of  the  gaps  in  our  knowledge  which  is  lament- 
able.' We  have,  however,  some  rough,  imperfect  data 
which  for  our  present  purposes  it  seems  to  me  are 
adequate,  and  the  results  of  the  study  of  these  will  be 
shown  by  the  next  series  of  pictures. 

But  let  us  pause  for  a  moment  to  consider  this 
singular  table.  It  shows  in  the  second  column  the 
number  of  days  required  for  each  species  of  animal 

TABLE  I' 


Days  Needed 
to  Double 
Weight. 

100  Parts  Mother's  Milk  Contain 

Species. 

Proteid. 

Ash. 

Lime. 

Phosphoric 
Acid. 

Man 
Horse 
Cow 
Goat 

Pig 
Sheep 
Cat 
Dog 
Rabbit      ' 

180 
60 

47 
19 
18 
10 

9* 

8 

7 

1.6 
2.0 

3-5 
4-3 
5.9 
6.5 
7.0 

7-3 
10.4 

0.2 
0.4 
0.7 
0.8 

0.9 
1.0 

1-3 
2.4 

0.0328 
0.124 
0.160 
0.210 

0.272 

0.453 
0.8914 

0.0473 
0.I3I 
0.197 
0.322 

0.412 

0.493 
0.9967 

indicated  at  the  left  to  double  its  weight  after  birth. 
A  man  takes  180  days  to  double  his  weight;  a 
horse,  60 ;  a  cow,  47  ;  a  goat,  19  ;  a  pig,  18  ;  a  sheep, 
10;  a  cat,  9^  ;  a  dog,  8;  a  rabbit,  6  (or  possibly  7 
days).  Now  here  are  analyses  of  the  milk.  The 
main  point  of  interest  is  to  be  found  in  the  figures  in 
the  third  column,  which  represent  the  amount  of  albu- 

^  After  Abderhalden,    Zeitschrift  fur  Physiologische  Chemie,  Band  XXVI., 
p.  497. 


io8  AGE,  GROWTH,  AND  DEATH 

minoid,  or  proteid  material  contained  in  the  milk. 
You  will  observe  that  for  man  the  proportion  is 
lowest,  1.6  per  hundred  parts;  the  horse  has  a  little 
more — 2  ;  cattle — 3.5  ;  and  so  the  values  run.  In 
other  words,  it  is  obvious  that  the  less  the  proteid  in  the 
milk,  the  longer  does  the  species  require  to  double  its 
weight.  This  looks  at  first  sight  as  if  there  were  a 
relation  between  the  composition  of  the  milk  and  the 
period  of  growth  of  the  animal ;  but  you  know  very- 
well  that  if  you  take  the  milk  of  a  cow,  which  is  very 
much  richer  in  proteid  material,  and  feed  it  to  a  baby, 
a  human  baby,  that  baby  does  not  grow  at  the  same 
rate  as  the  young  cow,  but  grows  at  the  human  rate. 
It  is  obvious,  therefore,  that  it  is  somewhat  more 
complicated  than  a  mere  question  of  food  supply. 
We  have  here  in  fact  one  of  the  beautiful  illustrations 
of  the  teleological  mechanism  of  the  body.  These  va- 
rious species  have  their  characteristic  rates  of  growth, 
and  by  an  exquisite  adaptation,  the  composition  of 
the  mother's  milk  has  become  such  that  it  supplies 
the  young  of  the  species  each  with  the  proper  quantum 
of  proteid  material  which  is  needed  for  the  rate  of 
growth  that  the  young  offspring  is  capable  of.  It  is 
a  beautiful  adjustment,  but  there  is  not  a  causal  rela- 
tion between  the  proteid  matter  of  the  mother's  milk 
and  the  rate  of  growth  of  the  young.  It  is  an  example 
of  correlation,  not  of  causation. 

We  pass  now  to  the  next  of  our  slides  (Fig.  37), 
which  carries  us  to  the  study  of  our  own  species.  It 
is  not  possible  at  the  present  time  to  represent  in  any 


THE  RATE  OF  GROWTH 


109 


form  of  curve,  which  I  have  seen,  the  daily  percentages 
of  increment  for  man  covering  the  whole  period  of 
growth.  In  order  to  get  the  results  together,  I  have 
confined  myself  here  to  the  representation  of  the 
yearly  percentages.  Now  from  the  age  of  zero  to 
the  age  of  one  year,  you  see  according  to  Table  II.,  a 
child  is  able  to  increase  its  weight  200  per  cent;  but 
from  the  end  of  the  first  to  the  end  of  the  second 


ZOOJi 


100% 


i07o 
10% 


•EAR5     I       2       3      4       5      6       7      8       9      10     II      12      13     14      15      16     17      18     19     20    21     22     23     24    25 

Fig.  37. 

year,  only  20  per  cent,  and  thereafter  it  fluctuates  in 
the  neighbourhood  of  10  per  cent  a  year  until  the 
aee  of  thirteen.     At   fourteen  or  fifteen  there   is  a 


no  AGE,  GROWTH,  AND  DEATH 

fluctuation,  an  increase,  and  then  tlie  decline  goes  on 
again,  and  slowly  we  see  the  growth  power  fading 
out*     Authors  are  not  agreed  as  to  the  exact  statis- 


20p% 


100% 


20% 

10% 


YEARS    12       3      4       5      6       7       e       9      10      II      12      13      14     15     16     17      18      19     20    21      22     23     24 

Fig.  38. 

tical  value,  and  so  I  will  ask  to  have  thrown  upon  the 
screen  another  curve  (Fig.  38),  also  representing  the 
percentage  increase  of  boys,  and  based  chiefly  upon 

'  The  curves  credited  to  Miihlmann  are  taken  from  his  very  excellent  memoir, 
Ueber  die  Ursache  des  Alters,  8vo,  Wiesbaden  (Bergmann),  190O  ;  see  specially 
p.  114.  His  tables  are  particularly  available  in  this  connection  because  he  has 
adopted  my  method  of  calculating  the  rate  of  growth,  but  he  does  not  present 
his  results  in  graphic  form. 


THE  RATE  OF  GROWTH 


English   tables.     For  Tables  II.   and  III.,   I  am   in- 
debted  to    my   friend   Professor   Donaldson,    of  the 

TABLE   II 

Growth  of  English  Boys 

(Compiled  by  H.  H.  Donaldson) 


ears. 

Weight 
in  Kilos. 

Yearly 

Percentage 

Increments. 

O 

3-2 

I 

99 

— 

3-2 

= 

6.7       - 

-       3.2 

= 

209.0  % 

2 

12.8 

— 

9.9 

= 

2.9       - 

-       9-9 

= 

29.0^ 

3 

15.4 

— 

12.8 

= 

2.6       - 

-     12.8 

= 

20.0  % 

4 

16.9 

— 

15-4 

= 

1-5     - 

-     15-4 

= 

9-7^ 

5 

18.1 

— 

16.9 

= 

1.2     - 

-     16.9 

= 

S-9% 

6 

20.1 

— 

18  I 

= 

2.0     - 

-     18.1 

= 

II. 0  % 

7 

22.6 

— 

20.1 

— 

2.5     - 

-     20.1 

= 

12.0  % 

8 

24.9 

— 

22.6 

=r 

2.3     - 

-     22.6 

= 

10.0% 

9 

27.4 

— 

24.9 

= 

2.5     - 

-     24.9 

= 

lO.O  % 

lO 

30.& 

— 

27.4 

= 

3-2     - 

-     27.4 

= 

11.6% 

II 

32.6 

- 

30.6 

= 

2.0    - 

-     30.6 

= 

6.5^ 

12 

34  9 

- 

32.6 

= 

2.3   - 

-     32.6 

= 

7.1^ 

13 

37-6 

— 

34-9 

=: 

2.7    - 

-     34-9 

= 

7-9^ 

14 

41.7 

— 

37-6 

= 

4.1    - 

-     37-6 

= 

11.0% 

15 

46.6 

— 

41-7 

= 

4.9   - 

-     41-7 

= 

11.7% 

i6 

53-9 

— 

46.6 

= 

7-3     - 

-     46.6 

= 

15.7^ 

17 

59.3 

— 

53-9 

= 

5-4     - 

-     53-9 

= 

lO.O^ 

i8 

62.2 

— 

59-3 

= 

2.9     - 

-     59-3 

= 

4.9^ 

19 

63.4 

- 

62.2 

= 

1.2     - 

-     62.2 

= 

1.9^ 

20 

64.9 

— 

63.4 

= 

1-5     - 

-     63.4 

= 

2.3^ 

21 

65.7 

— 

64.9 

= 

0.8     - 

-     64.9 

= 

1.2  % 

22 

67.0 

— 

65.7 

= 

1-3     - 

-     65.7 

= 

1-9% 

23 

67. 

— 

67. 

= 

.0     - 

-     67.0 

= 

.0% 

24 

67. 

- 

67- 

= 

.0     - 

-     67.0 

=: 

.0% 

Wistar  Institute  in  Philadelphia.^     He  finds  in  these 

'  Compare  Donaldson,  The  Growth  of  the  Brain,  London,  1895,  pp.  51  and 
63.  Professor  Donaldson  has  had  the  kindness  to  revise  his  tables  and  allow 
me  to  use  them.  They  are  given  in  the  text.  The  following  extract  from  his 
letter  of  January  23,  1907,  refers  to  the  tables  as  herewith  printed  : 

"  I  shall  be  very  glad  to  let  you  make  any  use  of  tables  or  diagrams  in  The 
Growth  of  the  Brain,  and,  to  facilitate  this,  I  enclose  the  calculations  for  the 


AGE,  GROWTH,  AND  DEATH 


records  an  increment  of  a  little  more  than  200  in  the 
first  year,  but  the  drop  comes  during  the  second  year 

TABLE  III 

Growth  of  English  Girls 

(Compiled  by  H.  H.  Donaldson) 


Years. 

Wei^jht 
in  Kilos. 

Yearly 

Percentage 

Increments. 

0 

3-1 

I 

9.1 

— 

3-1 

= 

6.0     - 

-       3-1 

= 

193        fo 

2 

11-5 

— 

9.1 

= 

2.4     - 

-       9-1 

= 

26       % 

3 

14.4 

— 

II. 5 

= 

2.9     - 

-     11-5 

= 

25        % 

4 

16.4 

— 

14.4 

= 

2.0     -= 

-     14.4 

= 

14       % 

5 

17.8 

— 

16.4 

= 

1.4     - 

-     16.4 

= 

S.Sfo 

6 

19.0 

- 

17.8 

= 

1.2     - 

-     17.8 

= 

b.lfo 

7 

21.6 

— 

19.0 

= 

2.6     - 

-     19.0 

— 

13-7  % 

8 

23.7 

— 

21.6 

= 

2.1     - 

-     21.6 

= 

9-1  % 

9 

25.3 

— 

23-7 

= 

1.6    - 

-     23.7 

— 

t.q% 

10 

28.2 

— 

25-3 

= 

29     - 

-     25.3 

= 

11.4^ 

II 

31.0 

— 

28.2 

= 

2.8     - 

-     28.2 

= 

9-9^ 

12 

34-7 

— 

31.0 

= 

3-7     - 

-     31-0 

= 

11.9^ 

13 

39-7 

— 

34-7 

= 

5-0     - 

-     34.7 

= 

14-4^ 

14 

44.0 

— 

39-7 

= 

4-3     - 

-     39-7 

= 

10.8^ 

15 

48.3 

— 

44.0 

= 

4.3     - 

-     44- 0 

= 

9.8^ 

16 

51-4 

— 

48.3 

= 

3-1     - 

-     48.3 

= 

6.4^ 

17 

52.5 

— 

51-4 

= 

I.I     - 

-     51-4 

— 

2.1  % 

18 

55.1 

— 

52.5 

= 

2.6     - 

H       52.5 

= 

4:9     fo 

19 

56-4 

— 

55.1 

— 

1.3     - 

-     55-1 

= 

2.3% 

20 

*56.i 

— 

56.4 

= 

.3     - 

-     56.4 

= 

.5^* 

21 

*55.5 

— 

56.1 

= 

.6     - 

-     56.1 

= 

I.O  %* 

22 

56.1 

— 

55-5 

= 

.6     - 

-     55.5 

= 

i.o% 

23 

56-4 

— 

56.1 

= 

•3     - 

-     56.1 

= 

o.S% 

*  Decrease. 

and  is  sta 

rtling 

in  its  enormous 

extent 

and 

is  contrastec 

percentages.  These  have  been  recently  revised  in  the  first  part,  in  the  following 
way.  In  .place  of  the  values  given  in  Roberts'  Tables,  I  have  introduced,  in 
the  males,  first  year,  where  he  leaves  a  blank,  the  following,  9.9  kilos,  and  in 
place  of  his  entry  for  the  second  year,  which  figures  14.5  kilos,  I  have  used  the 
value  12.8.  These  two  values,  9.9  and  12.8,  are  taken  from  Camerer.  They 
are  based  on  three  cases  in  each  instance  (Camerer,  W.,  '9  •,  '  Untersuchungen 


THE  RATE  OF  GROWTH 


113 


with  the  later  less   decline.     The    phenomena    may 
well  arouse  our  attention   and  convince  us  that  we 


200)^ 


iOO% 


20% 


le^  ^^n.cte'fneyrvtii' ^cfu 


17      18      19     20    21     22     23 


Fig.  39. 


are  approaching  a  most  important  scientific  question, 
the  question  of  why  the  drop  comes  in  this  way.  In 
the  case  of  girls,  as  the  next  of  our  slides  will  show, 

ueber  Massenwachsthum  und  Laengenwachsthuni,'  yahrbuch  f.  Kinderkeil- 
kunde,  Bd.  XXXVI.,  pp.  249-293,  1893). 

"  These  calculations  represent  weights  without  clothing,  whereas  my  under- 
standing of  Roberts'  Tables  is  that,  with  the  exception  of  the  weight  at  birth, 
his  values  represent  weights  with  clothing  ;  although  I  imagine  the  statement 
would  not  bear  very  careful  investigation.  I  have  not  attempted  in  turn  to 
correct  Camerer's  records  by  adding  the  amount  due  for  clothing,  which, 
however,  could  be  done  by  the  use  of  Bowditch's  Tables." 


114 


AGE,  GROWTH,  AND  DEATH 


we  can  prove  the  same  phenomena  with  sHghtly  dif- 
ferent vakies.  Girls,  Hke  the  females  of  other  species, 
grow  a  little  less  forcibly  (Fig.  39)  than  boys.  They 
do  not  quite  attain  a  200  per  cent,  value  for  the  first 
year,  but  they  too  drop  in  a  similar  manner  to  the  boys 
to  about  30  per  cent,  and  away  down  towards  10  per 


100% 


10% 


EARS      1        Z        34        5       6       7       8       9       10      II       12       13      14      15      16       17      18      19     20     21      22     23 

Fig.  40. 

cent,  in  the  third  year.  Then  comes  the  long  slow 
gradual  decline  up  to  the  period  of  twenty-three.  Pro- 
fessor Donaldson,  as  our  next  slide  will  demonstrate 
to  us,  has  prepared  curves  (Fig.  40)  from  the  English 


THE  RATE  OF  GROWTH  115 

figures  for  girls  also.  They  come  up  nearer  to  the 
200  per  cent  than  in  Muhlmann's  table,  but  drop 
well  below  30  per  cent,  in  the  second  year,  and  down 
to  20  per  cent,  in  the  fourth.  Then  occurs  the  slight 
increase  of  growth  in  the  period  of  twelve,  thirteen, 
fourteen  years,  and  next  the  final  stage  of  decline. 
In  the  four  cases  the  human  rate  curve  is  similar. 
The  great  fall  takes  place  at  the  beginning,  the  slow 
fall  towards  the  end.  Professor  Thoma^  has  thought 
he  could  get  somewhat  more  accurate  results  by 
putting  boys  and  girls  together,  and  he  has  made  a 
calculation,  as  shown  now  upon  the  screen,  of  a  curve 
in  which  the  two  sexes  are  combined.  His  figures 
again  differ  somewhat  from  those  we  have  considered, 
but  you  meet  in  this  curve(Fig.  4i)also  the  same  general 
phenomena.  There  is  an  enormous  percentage  of 
growth  during  the  first  year  ;  an  enormous  drop  dur- 
ing the  second  ;  then  the  slow  decline  ;  the  moderate 
fluctuation  upward  ;  and  then  the  last  slow  disappear- 
ance of  growth.  In  every  instance,  therefore,  we  have 
an  absolute  demonstration,  it  seems  to  me,  of  the 
strange  phenomenon.  Paradoxical  it  will  sound, 
whenever  it  is  first  stated  to  any  one,  that  the  period 
of  youth  is  the  period  of  most  rapid  decline ;  that  the 
period  of  old  age  is  that  in  which  decline  is  slowest. 

'  R.  Thoma,  Untersuchimgen  ueber  die  Grosse  7m d  das  Gemcki  der  anatojh- 
ischen  Bestandtheile  des  menschlichen  Korpers,  Leipzig,  8vo,  1882,  Tabelle 
XXVIII.,  p.  149. 

Professor  Thoma  gives  only  the  usual  data,  the  averages  and  first  differences. 
From  them  I  have  calculated  the  percentage  increments,  in  accordance  witli 
which  the  curve.  Fig.  40,  has  been  constructed.  Thomas  table  is  based  cm 
Quetelet's  measurements. 


ii6 


AGE,  GROWTH,  AND  DEATH 


We  shall  learn  in  the  next  lecture  that  this  double 
phenomenon  furnishes  us  a  clue  to  further  investiga- 
tions, and  leads  to  certain  new  inquiries,  which  enable 


100% 


30% 


0xn^  ycz^n^  ^L^UA^ 


e        9       10       It        \Z       13      14       IS      16      17        18       19      20     Zl      ZZ      23     24     23 


Fig.  41. 


US  to  gain   some   further   insight   into   the  essential 
nature  of  the  phenomena  of  age. 

It  can  also  be  demonstrated  that  the  decline  in  the 
growth  power  is  proceeding  during  the  first  year  of 


THE  RATE  OF  GROWTH  117 

life.  Taking  the  observations  recorded  by  Bouchaud,^ 
the  following  table  has  been  calculated  by  Muhlmann 
(/.<;.,  p.  112).  It  is  only  necessary  to  look  at  the 
diminishinof  values  in  the  third  column  to  recoQfnise 
the  swift  decline  in  the  rate  of  growth. 


TABLE  IV 

Age  in 
Months. 

Weight 
in  Grammes. 

Monthly- 
Percentage 
Increment. 

0 

3250 

I 

4000 

23.0 

2 

4700 

17-5 

3 

5350 

14.0 

4 

5950 

II. 0 

5 

6500 

9.2 

6 

7000 

7-7 

7 

7450 

6.4 

8 

7850 

5.3 

9 

8200 

4-4 

10 

8500 

3.6 

11 

8750 

30 

12 

qOOO 

2.8 

This  completes  the  series  of  curves  which  I  had 
prepared  to  present  to  you  to  show  the  rate  of  growth 
in  animals  from  their  birth  only,  but  of  course  there 
has  been  also  a  growth  of  the  animals  which  preceded 
their  birth,  and  that  now  must  briefly  be  considered. 

The  mere  inspection  of  developing  embryos  of 
known  ages  gives  us  some  idea  of  the  rate  of  growth. 
With  the  aid  of  the  lantern  I  will  ask  you  to  look  with 
me  at  some  pictures  of  the  developing  chick  and  de- 
veloping rabbit.   Let  us  begin  with  the  chick  (Fig.  42).^ 

'  Bouchaud,  De  la  inort  par  inanition  et  etude  experimentale  sur  la  nutrition 
chez  le  nouveau-n^,  1864. 

^  During  the  lectures  a  series  of  lantern  slides  were  projected  upon  the 
screen,   made  from  photographs   of    mounted  specimens  of  chicken  embryos, 


ii8  AGE,  GROWTH,  AND  DEATH 

We  have  first  an  embryo  of  twenty  hours  of  incu- 
bation, No.  i;  following  it  one  of  one  day,  No.  2. 
You  can  observe  just  a  little  line  of  structure  indi- 
cated and  showing  where  the  longitudinal  axis  is  to 
be  situated.  By  the  second  day,  No.  3,  the  chick  has 
distinctly  a  head  and  a  little  heart,  and  those  who  are 
expert  can  differentiate  with  a  microscope  the  axis  of 
the  body,  the  beginning  of  the  formation  of  the  intes- 
tine and  of  the  muscles.  At  the  end  of  the  first  day 
there  was  little  more  than  a  mere  gathering  of  cells, 
but  during  the  twenty-four  hours  of  the  second  day  the 
gathering  has  changed  from  a  mere  streak  upon  the 
surface  of  the  yolk  to  a  well-formed  individual,  with 

which  showed  very  clearly  the  progress  of  development  in  the  chick  during  the 
very  early  stages.  The  first  figure  illustrated  a  chick  of  eighteen  hours'  in- 
cubation. The  embryo  had  been  skimmed  off  from  the  surface  of  the  egg, 
hardened,  coloured  artificially,  and  mounted  in  the  manner  of  the  ordinary 
microscopical  preparation  in  Canada  balsam.  At  this  age  the  naked  eye  can 
just  distinguish  a  line,  which  indicates  the  position  of  the  axis  of  the  embryo. 
The  unaided  eye  can  recognise  nothing  more.  In  the  second  picture  the  head 
and  neck  of  the  embryo  were  easily  distinguishable,  and  a  few  of  the  earliest 
primitive  segments.  The  third  slide  showed  a  stage  of  a  day  and  a  half.  The 
spinal  cord  and  brain  were  distinctly  differentiated,  and  numerous  so-called 
"  blood  islands"  scattered  about.  The  final  slide  of  the  series  showed  a  chick 
of  three  and  one  half  days.  It  has  not  seemed  necessary  to  reproduce  these 
figures  with  the  present  text,  as  they  merely  duplicate,  on  a  larger  scale  and 
with  more  detail,  the  pictures  which  have  been  included. 

Explanation  of  Fig.  42. 
Ten  Stages  of  the  Developing  Chick,  after  Franz  Keibel's  Normentafcln. 
All  the  figures  are  magnified  four  diameters.      In  No.  i  only  the  parts  indicated 
in  the  vertical  axis  of  the  figure  correspond  to  embryonic  structures  proper. 
No.  I.  Incubated  20  hrs.  No.    6.  Incubated  3  days,  16  hrs. 

No.  2.         "  24  hrs.  No.     7.  "         4  days,  8  hrs. 

No.  3.  "  2  days.  No.     8.  "  5  days,  i  hr. 

No.  4.         "  2  days,  19  hrs.       No.    g.  "  7  days,  4  hrs. 

No.  5.  "  2  days,  22  hrs.       No.  10.  "  8  days,  I  hr. 


I20  AGE,  GROWTH,  AND  DEATH 

recognisable  parts  and  several  times  the  volume  it  had 
when  one  day  old.  The  next  figures,  Nos.  4  and  5, 
illustrate  the  alteration  which  occurs  during,  approx- 
imately, the  third  day.  It  is  obvious  that  the  embryo 
has  again  made  an  enormous  increase  in  volume. 
The  eye  has  developed,  the  heart  has  become  large, 
the  tail  is  projecting,  the  dorsal  curve  of  the  future 
neck  is  distinguishable.  We  pass  next  to  the  fourth 
day.  No.  6.  Is  it  not  a  strange  looking  beast,  with 
its  wing  here  and  leg  there,  a  little  tail  at  this  point ; 
an  enormous  eye,  almost  monstrous  in  proportion  ; 
and,  finally,  here  a  great  bulge  caused  by  the  middle 
division  of  the  brain.  After  five  days,  Nos.  7  and  8, 
we  have  a  chick  the  brain  of  which  is  swelling,  causing 
the  head  to  be  of  so  queer  a  shape  that,  with  the 
eye  which  seems  out  of  all  proportion  to  the  rest  of 
the  body,  it  imparts  an  uncanny  look  to  the  embryo. 
The  wing  is  shaping  itself  somewhat,  and  the  ends  of 
the  leg,  we  can  see,  will,  by  expansion,  form  a  foot. 
Finally,  the  chick  after  seven,  No.  9,  and  after  eight 
days,  No.  10,  is  figured.  In  the  short  interval  of  only 
six  days  the  chick  grows  from  the  size  represented  by 
No.  2  to  that  shown  in  the  last  figure  upon  the  plate. 
It  is  an  enormous  increase.  Suppose  a  chick  after  it 
was  born  were  to  grow  at  such  a  rate  as  that !  The 
eight-day  embryo  is  perhaps  thirty  or  forty  times  as 
big  as  it  was  six  days  before.  It  would  seem  marvel- 
lous to  us  if  a  chick  after  it  was  hatched  should  become 
in  six  days  thirty  times  as  large  and  heavy  as  when 
it  first  came  out  from  the  ^gg.     It  is  perhaps  advis- 


THE  RATE  OF  GROWTH 


able  to  let  you  follow  the  growth  of  the  chick  a  little 
farther,  and  accordingly  I  present  another  picture 
(Fig.  43),  which  shows  an  embryo  of  about  ten  days. 
The  little  marks  upon  the  surface  of  these  embryos 


Fig.  43.     A  Chick  Removed  from  an  Egg  which  had  been  Incubated 
10  Days  and  2  Hours.     Magnified  four  diameters.     After  Keibel. 

indicate  the  commencing  formation  of  the  feathers. 
A  comparison  of  the  series  of  figures  proves  that  the 
development  is  taking  place  with  marvellous  speed. 
We  need  only  to  look  at  these  stages,  comparing  them 


122  AGE,  GROWTH,  AND  DEATH 

with  one  another,  to  realise  that  the  progress  of  the 
embryo  in  size  and  development  proceeds  with  a 
rapidity  which  is  never  to  be  found  in  later  stages. 

The  history  of  embryonic  rabbits  declares  with 
equal  emphasis  that  the  earliest  development  is  ex- 
tremely rapid.  I  wish  now  to  show  you  a  series  of 
pictures  to  illustrate  in  the  same  manner  the  pro- 
gressive development  of  the  rabbit.  Numbers  one  to 
five  of  the  figures  upon  the  screen  represent  what  is 
known  as  the  germinal  area,  in  the  centre  of  which 
the  actual  embryo  is  gradually  formed.  In  No.  i 
merely  the  axis  is  indicated,  in  front  of  and  alongside 
of  which  the  parts  of  the  embryo  are  to  arise,  as  is 
suggested  by  Nos.  2,  3,  4,  5.  These  stages  cover  the 
seventh  and  eighth  days.  Nos.  6  to  14  figure  actual 
embryos.  No.  6  of  nine  and  a  half,  No.  14  of  fifteen 
days.  No.  6  is  singularly  twisted  into  a  spiral  form, 
the  reason  for  which  is  still  undiscovered.  No.  9 
shows  the  condition  at  eleven  days — notice  the  limbs, 
a  leg  in  front  and  a  leg  behind,  each  only  a  small 
mound  as  yet  upon  the  surface  of  the  body ;  the  dis- 

EXPLANATION   OF  FiG.    44. 

Fourteen  Stages  of  the  Developing  Rabbit,  after  Minot's  and 
Taylor's  "  Normal  Plates."  All  the  figures  are  magnified  four  diameters. 
Nos.  2  to  5  are  irregular  as  to  age,  but  show  successive  stages  of  development. 
The  early  development  is  extremely  variable  and  the  observations  do  not  yet 
suffice  to  determine  the  average  typical  condition  for  each  day  under  nine. 
No.  I.  Embryo  of  7^  days.  No.    8.  Embryo  of  10^  days. 


No.  2. 

"           8X     " 

No.    9. 

II 

No.  3. 

"           8X     •• 

No.  10. 

llVz 

No.  4. 

8 

No.  II. 

12% 

No.  5. 

8>^     " 

No.  12. 

13 

No.  6. 

9^/2     " 

No.  13. 

^4 

No,  7. 

.»                            JQ                             H 

No,  14. 

15 

124  AGE,  GROWTH,  AND  DEATH 

tinct  eye,  the  protuberance  caused  by  the  heart.  Nos. 
1 1  and  12  show  the  embryonic  shape  at  twelve  and  a 
half  and  at  thirteen  days — there  has  been  a  great  in- 
crease of  size  with  accompanying  modifications  of 
form.  The  next  pair,  Nos.  13  and  14,  present  us  em- 
bryos of  fourteen  and  fifteen  days,  respectively,  and 
you  see  that  the  growth  is  very  marked  indeed,  and 
the  change  of  form  obvious  ;  the  creature  is  now  pass- 
ing from  the  embryonic  type  into  something  resem- 
bling a  rabbit.  Other  pictures  could  readily  be  added, 
but,  though  two  weeks  must  still  elapse  before  the 
animal  will  be  ready  to  enter  the  world,  it  is  not  neces- 
sary for  my  present  purpose  to  include  this  period  in 
our  survey.  We  need  only  contemplate,  it  seems  to  me, 
the  series  of  drawings  in  Fig.  44  to  realise  that  the  early 
embryonic  growth  of  the  rabbit,  like  the  embryonic 
growth  of  the  chick,  proceeds  with  a  speed  which  is 
never  paralleled  by  the  growth  during  later  stages. 

Now  I  had  a  considerable  number  of  rabbit  em- 
bryos preserved  in  alcohol,  and  though  it  was  not  very 
accurate  to  weigh  them  as  alcoholic  specimens,  in  or- 
der to  determine  their  true  weight,  yet  I  resolved 
to  do  so  as  it  was  the  best  means  at  my  disposal  at 
the  time.  The  result  of  that  weighing  was  very  in- 
teresting to  me,  becaused  it  showed  that  in  the  period 
of  nine  to  fifteen  days  the  rabbits  had,  on  an  average, 
added  704  per  cent,  to  their  weight  daily ;  but  in  the 
period  of  from  fifteen  to  twenty  days,  the  addition  is 
very  much  less  than  this,  only  212  per  cent.  But 
these  rabbits  at  ten  days  have  already  had  a  consid- 


THE  RATE  OF  GROWTH  125 

erable  period  of  development  behind  them,  and  as  we 
have  discovered  that  the  younger  the  animal  the  more 
rapid  its  growth,  we  are  safe,  it  seems  to  me — since 
we  have  learned  that  from  the  tenth  to  the  fifteenth 
day  there  is  a  daily  increase  of  over  700  per  cent. — 
in  assuming  that  in  yet  younger  rabbits  an  increase 
of  1000  per  cent,  per  day  actually  occurs.  That  is 
not  so  extraordinary  an  assumption,  for  bacteria  are 
known  to  divide  every  half-hour,  and  if  the  little 
bacterium  divides  and  grows  up  to  full  size  in  half  an 
hour,  and  then  divides  again,  it  means  that  within 
a  half-hour  one  bacterium  has  become  two,  and  has 
increased,  obviously,  100  per  cent.;  and  if  those  two 
ao^ain  divide  as  before,  we  should  have  four  bacteria 
at  the  end  of  an  hour — an  increase  of  400  per  cent, 
and  at  the  end  of  another  half-hour,  of  800  per  cent., 
and  so  on  ever  in  geometrical  progression.  We  learn, 
then,  that  bacteria  may  in  a  few  hours  add  1000  per 
cent,  to  their  original  weight,  and  it  is  not  by  any 
means  an  exorbitant  demand  upon  our  credulity  to 
accept  the  conclusion  that,  in  their  early  stages,  rabbits 
and  other  mammals  and  birds  are  capable  of  growing 
at  least  1000  per  cent,  a  day.  If  this  be  true,  and  it 
doubtless  is  true,  we  can  adopt  it  as  a  convenient 
basis  for  comparison.  As  we  learned  from  the  rate 
curves,  which  were  projected  upon  the  screen  earlier 
during  the  hour,  the  male  rabbit  gains  in  one  day 
shortly  after  birth  nearly  eighteen  per  cent. — seven- 
teen and  four  tenths  per  cent. — and  the  female  rabbit 
gains    nearly    seventeen    per    cent.      Now    we     can 


126  AGE,  GROWTH,  AND  DEATH 

estimate  the  loss  very  simply  by  deducting  this  rate, 
which  is  the  capacity  of  the  animal  to  grow  persisting 
at  birth,  from  its  original  capacity,  which  we  assume 
to  have  been  looo  per  cent,  per  day.  And  if  we  do 
that  the  result  is  obvious.  Over  98  per  cent,  of  the 
original  growth  power  of  the  rabbit  or  of  the  chick 
has  been  lost  at  the  time  of  birth  or  hatching,  respec- 
tively, and  the  same  thing  is  equally  true  of  man. 
We  start  out  at  birth  certainly  with  less  than  two  per 
cent,  of  the  original  growth  power  with  which  we 
were  endowed.  Over  98  per  cent,  of  the  loss  is 
accomplished  before  birth — less  than  two  per  cent, 
after  birth.  That,  I  think,  Is  a  rather  unexpected  con- 
clusion, certainly  not  one  which,  until  I  began  to 
study  the  subject  more  carefully,  I  in  the  least  ex- 
pected ;  and  even  now  when  I  have  become  more 
familiar  with  It,  it  still  fills  me  with  astonishment,  it  is 
so  different  from  the  conception  of  the  process  of  de- 
velopment as  we  commonly  hold  it,  so  different  from 
our  conclusions  based  on  our  acquaintance  with  the 
growth  and  progress  of  the  individuals  about  us.  We 
overlook  the  fact  that  the  progress  which  each  indi- 
vidual makes  is  the  result  of  accumulation.  It  is  as 
if  money  were  put  into  the  savings-bank;  it  grows  and 
becomes  larger,  but  the  rate  of  interest  does  not  alter. 
So  too  with  us;  we  see  there  is  an  accumulation  of 
this  wealth  of  organisation  which  gives  us  our  mature 
power.  But  as  that  accumulation  goes  on,  our  body 
seems  to  become,  as  it  were,  tired.  We  may  com- 
pare it  to  a  man  building  a  wall.      He  begins  at  first 


THE  RATE  OF  GROWTH 


127 


600/„ 


SOO/i 


400% 


300% 


200% 


with  great  energy,  full  of  vigour ;  the  wall  goes  up 
rapidly ;  and  as  the  la- 
bour continues  fatio^ue 
comes  into  play.  More- 
over, the  wall  grows 
higher,  and  it  takes 
more  effort  and  time  to 
carry  the  material  up  to 
its  top,  and  to  continue 
to  raise  its  heigfht,  and 
so,  as  the  wall  grows 
higher  and  higher,  it 
grows  more  slowly  and 
ever  more  slowly,  be- 
cause the  obstacles  to 
be  overcome  have  in- 
creased with  the  very 
height  of  the  wall  itself. 
So  it  seems  v/ith  the  in- 
crease of  the  orofanism  ; 
with  the  increase  of  our 
development,  the  ob- 
stacles to  our  growth 
increase.  How  that  is  I 
shall  hope  to  explain  to 
you  a  little  more  clearly 
in  the  next  lecture. 

We  have  one  more 
slide,  which  I  would 
like  to  show  you 


Fig.  45. 

It  indicates  the  rate  of  erowth  in 


128  AGE,  GROWTH,  AND  DEATH 

man  before  birth  as  far  as  it  can  be  determined  without 
better  knowledge  than  "I  have  at  command.  The  time 
intervals  in  the  diagram  correspond  to  the  so-called 
lunar  months — the  ten  lunar  months  of  prenatal  life. 
Of  our  early  development  we  know  very  little  so  far 
as  statistics  are  concerned,  but  from  the  third  month 
onward  we  have  some  records.  It  is  found  that  from 
the  third  to  the  fourth  month  the  increase  is  600  per 
cent.  Just  contrast  that  with  200  per  cent,  added  in  one 
year  after  birth  ;  600  per  cent,  in  one  month  against  200 
per  cent,  in  one  year.  From  the  fourth  to  the  fifth 
month  it  is  scarcely  over  200  per  cent.  It  then  becomes 
only  a  little  more  than  100.  In  the  seventh  month,  less 
than  100  ;  and  finally  in  the  ninth  and  tenth  months,  it 
becomes  very  small  indeed,  less  than  20,  so  that  during 
the  prenatal  life  of  man,  as  we  have  seen  in  the  prenatal 
life  of  the  rabbit  and  of  the  chick  the  decline  in  the 
power  of  growth  is  going  on  steadily  all  the  time. 

I  shall  use  the  few  remaining  moments  to  report 
to  you  yet  another  bit  of  evidence  of  the  originally 
enormous  power  of  growth.  It  has  been  estimated 
that  the  germ  of  the  mammal,  with  which  the  devel- 
opment commences,  has  a  weight  of  0.6  milligram; 
another  estimate  which  I  have  found  is  of  0.3  milli- 
gram.'' Perhaps  I  can  give  you  some  idea  of  what 
this  value  means  by  telling  you  that  if  the  weight  of 
the  original  germ  of  a  mammal  is  assumed  to  be  0.6 

'  These  estimates  refer  to  the  placental  mammals  only.  My  authorities  are 
M.  Muhlmann,  Ueber  die  Utsache  des  Todes,  1900,  p.  45,  and  Donaldson, 
Growth  of  the  Brain,  1895,  p.  60. 


THE  RATE  OF  GROWTH  129 

milligram,  we  could,  according  to  the  laws  of  the  United 
States,  send  50,000  such  germs  by  letter  postage  for 
two  cents.  It  would  take  50,000  germs  to  make  the 
weight  of  one  letter.  That  perhaps  will  give  you 
some  impression  of  the  extreme  minuteness  of  the 
primitive  germ.  In  the  human  species  at  the  end  of 
even  a  single  month  it  is  no  longer  merely  a  germ, 
but  a  young  human  being,  very  immature,  of  course, 
in  its  development,  but  already  very  much  larger.  I 
doubt — even  after  all  that  I  have  said  this  evening 
about  the  startling  figures  of  growth  for  the  earlier 
stages — I  doubt  if  you  are  prepared  for  the  fact  that 
the  growth  of  the  germ  up  to  the  time  of  birth  repre- 
sents an  increase  of  over  five  million  per  cent.  How 
much  over  five  million  per  cent,  we  cannot  calculate 
accurately,  because  we  do  not  know  accurately  the 
weight  of  the  original  germ,  but  an  increase  of  five 
million  per  cent,  is  not  above  the  true  value.^  Con- 
trast that  with  anything  which  occurs  in  the  later 
periods.  What  a  vast  change  has  happened  !  What 
an  imrriense  loss  has  taken  place  !  The  rate  of  this 
loss  is  evidently  diminishing.  The  loss  occurs  with 
great  rapidity  in  the  young — less  rapidly  the  older 
we  become. 

Professor  Richard  Hertwig  of  Munich ~  has  reached 
a  similar  result  by  a  different  method  of  calculation. 
He  estimates   the   volume  of   the   human    fertilised 

'  Assuming  the  germ  to  weigh  0.0006  gramme,  and  the  child  at  birth  3200 
grammes,  the  percentage  increment  would  be  5,400,000. 

'^  R.  Hertwig,  "  Ueber  die  Ursache  des  Todes,"  reprinted  from  Allgemeine 
Zeitung,  Dec.  12,  13,  igo6  {Beilage). 


I30  AGE,  GROWTH,  AND  DEATH 

ovum  at  0.004  cubic  millimetre  and  of  the  child  at 
birth  at  3  to  4,000,000  cubic  millimetres,  a  billion 
times  increase.  Assuming  the  weight  of  a  man 
of  twenty  years  at  130  pounds,  the  increase  after 
birth  would  be  as  1:16.  He  thereupon  emphasises 
the  enormous  diminution  of  cell  production  which 
must  be  assumed.  It  is  a  pleasure  to  have  my  own 
views  confirmed  by  so  distinguished  a  colleague. 

I  attempted  to  convince  you  in  the  first  and  second 
lectures  that  that  which  we  called  the  condition  of 
old  age,  is  merely  the  culmination  of  changes  which 
have  been  going  on  from  the  first  stage  of  the  germ 
up  to  the  adult,  the  old  man  or  woman.  All  through 
life  these  changes  continue.  The  result  is  senility. 
But  if,  as  the  phenomena  of  growth  indicate  to  us  so 
clearly,  it  be  true  that  the  decline  is  most  rapid  at 
first,  then  we  must  expect  from  the  study  of  the  very 
young  stages  to  find  a  more  favourable  occasion  for 
analysis  of  the  factors  which  bring  about  the  loss  in 
the  power  of  growth  and  of  change  as  the  final  result 
of  which  we  encounter  the  senile  org-anism.  Not 
from  the  study  of  the  old,  therefore,  but  from  the 
study  of  the  very  young,  of  the  young  embryo,  and  of 
the  germ,  are  we  to  expect  insight  into  the  compli- 
cated questions  which  we  have  begun  to  consider  to- 
gether. I  shall  hope  in  the  next  lecture  to  prove 
to  you  that  the  supposition  which  has  guided  my  own 
observations  is  correct,  and  to  be  able  to  show  you 
that  we  do  actually,  from  the  study  of  the  developing 
embryo,  glean  some  revelations  of  the  cause  of  old  age. 


IV 


DIFFERENTIATION    AND    REJUVENATION 

TADIES  AND  GENTLEMEN:  In  order  to 
present  the  subject  of  this  evening,  I  will  take  a 
few  brief  moments  at  the  beginning  to  review  the 
results  reached  in  the  previous  lecture.  I  spoke  then 
of  the  phenomena  of  growth  and  endeavoured  to  make 
clear  to  you  what  I  consider  the  fundamental  con- 
ception of  this  study — that  the  decline  in  the  growth 
power  is  extremely  rapid  at  first  and  slow  afterwards. 
This  change  in  the  rate  of  growth  is  of  course  due  to 
things  in  the  animal  body  itself.  It  is  a  logical  con- 
clusion for  us  to  draw  that  if  we  are  to  study  out  the 
cause  of  the  loss  of  growth  power,  we  should  do  it 
rather  at  that  period  of  development  when  the  change 
in  the  rate  of  growth  is  most  rapid,  for  then  we  should 
expect  those  modifications  to  exhibit  themselves  most 
clearly  because  the  magnitude  of  cause  is  likely  to  be 
proportionate  to  the  magnitude  of  result,  or,  in  other 
words,  when  the  decline  is  most  rapid,  then  we  must 
expect  to  find  the  alterations  which  cause  that  decline 
in  the  organism  to  show  themselves  most  conspicu- 
ously. You  will  remember,  further,  that  we  spoke  of 
growing  old  as  being  a  much  more  complicated  ques 

131 


132  AGE,  GROWTH,  AND  DEATH 

tion  than  one  of  growth  alone,  and  that  there  occur, 
as  the  years  advance,  changes  in  the  structure  of  the 
body.  It  is  convenient  to  use  one  collective  term  for 
all  these  phenomena  of  becoming  old,  and  that  term, 
established  by  long  usage,  is  senescence,  the  becoming 
old.  What,  therefore,  we  have  to  search  for  at 
present  is  a  cause,  a  proximate  cause  at  least,  of 
senescence.  In  order  to  make  the  view  I  am  to  bring 
forward  this  evening  quite  clear  to  you,  I  must  first 
of  all  take  advantage  of  your  kindness  and  recapitu- 
late briefly  what  I  said  in  regard  to  cells,  for  you  will 
remember  that  the  cell  is  the  foundation  and  unit  of 
organic  structure.  With  your  permission  I  should 
like  to  recall  more  exactly  to  your  minds  what  I  said 
of  the  cells  by  having  thrown  upon  the  screen  the 
slide  which  we  saw  before  and  which  we  used  as  an 
illustration  of  the  cell.  Here  is  the  picture.  Above 
we  see  the  typical  cell  (No.  i)  from  the  oral  epithelium 
of  the  salamander,  and  you  remember  in  the  centre 
this  more  conspicuous  body  with  a  granular  and 
reticulated  structure  which  we  called  the  nucleus, 
and  surrounding  it  is  this  mass  which  we  called  the 
body  of  the  cell,  or  the  protoplasm.  Here  (No.  2)  is 
another  condition  of  a  cell  of  the  skin  of  the  salaman- 
der in  which  the  nucleus  presents  a  slightly  different 
appearance.  Here  also  we  have  quite  a  body  of  proto- 
plasm about  the  nucleus.  Every  cell  consists  of  these 
two  essential  and  fundamental  parts,  the  nucleus  and 
the  protoplasm.  Now  the  conclusion  to  which  I  shall 
gradually  bring  you  by  the  facts  to  be  laid  before  you 


L 


/o 


Fig.  46.  Cells  from  the  Mouth  (Oral  Epithelium)  of  the  Sala. 
MANDER. — After  Sobotta.  i,  recticulate  stage  ;  2,  skein  stage  ;  3,  4,  formation 
of  the  chromosomes  ;  5,  6,  formation  of  the  equatorial  plate  ;  7,  8,  division 
and  migration  of  the  chromosomes  ;  9,  reconstitution  of  the  two  daughter 
nuclei  ;  10,  completed  division  into  two  cells. 

133 


E34  AGE,  GROWTH,  AND  DEATH 

this  evening  is  that  the  increase  of  the  protoplasm, 
together  with  its  differentiation,  is  to  be  regarded  as 
the  explanation  (or  should  we  say  cause)  of  sen- 
escence. Though  protoplasm  is  the  physical  basis  of 
life,  though  it  is  the  actual  living  substance  of  the 
body,  its  undue  increase  beyond  the  growth  of  the 
nucleus  changes  the  proportions  of  the  two,  and  that 
change  of  proportion  causes  an  alteration  in  the  con- 
ditions of  the  living  cell  itself,  and  that  alteration  I  in- 
terpret, as  I  shall  explain  more  accurately  later,  as  the 
cause  of  senescence,  as  the  fundamental  cause  of  old 
age.  This  slide  (Fig.  46)  also  shows  to  us  the  early 
development  of  the  cells  through  those  phases  which 
result  in  the  multiplication  of  them.  The  nucleus 
changes  in  appearance  and  becomes  a  very  different 
looking  structure.  These  changes  I  need  not  now  go 
through  again.  Suffice  it  to  say  that  after  the  com- 
plicated alterations  have  completed  their  cycle,  we  get 
in  the  place  of  a  single  cell,  two,  and  each  has  its  own 
nucleus,  and  each  its  own  protoplasm.  Notice  here 
that  the  two  cells  (No.  10)  which  finally  result  are 
smaller  than  the  original  cells  from  which  they 
sprang,  'i'hese  are  by  no  means  imaginary  pictures, 
but  accurate  microscopic  drawings  from  real  cells  of 
the  salamander.  The  two  cells  which  are  thus  pro- 
duced from  one  parent  cell  are  characterised  by  their 
smaller  size,  and  this  smaller  size  applies  not  only  to 
the  cell  as  a  whole,  but  likewise  to  its  nucleus.  After 
having  been  thus  reduced  in  size,  the  nuclei  and  the 
cells  will  both  expand,  and  soon  the  daughter  cells 


DIFFERENTIATION  AND  REJUVENATION    135 

will  return  to  the  mother  dimension  and  be  as  large 
as  the  parent  cell  from  the  division  of  which  they 
arose.  There  is  thus,  we  learn,  the  constant  fluctua- 
tion in  the  size  of  cells,  a  fluctuation  in  their  di- 
mensions accompanying  the  process  of  cell  division. 
Presently  we  shall  have  more  to  say  in  regard  to 
this  matter  of  the  change  in  the  cell  in  size.  The 
next  picture  (Fig.  47)  which  I  want  to  recall  to  you 
is  one  which  we  also  had  in  an  earlier  lecture.  It 
represents  three  slices  through  a  very  young  rabbit 
before  any  of  the  organs  of  the  animal  have  begun 
to  develop.  We  can  see  here  clearly  the  nuclei,  as  I 
pointed  out  to  you  before,  nearly  uniform  in  struc- 
ture, and  you  notice  that  the  protoplasm  around  each 
nucleus  is  quite  small  in  amount.  If  you  will  recall 
the  previous  picture  (Fig.  46)  of  the  skin  of  the  sala- 
rhander,  upon  the  screen  a  moment  ago,  you  will 
realise  immediately,  in  comparing  the  two,  that  in 
these  young  cells  the  proportion  of  the  protoplasm  to 
the  nucleus  is  very  small.  That  is  again  one  of  the 
fundamental  facts  to  which  we  shall  recur  in  a  mo- 
ment. I  wanted  to  show  you  this  picture  in  order 
to  revive  in  your  minds  the  conception  which  I  en- 
deavoured to  give  you  before  of  the  undifferentiated 
tissue,  where  the  cells  have  nuclei  pretty  uniform  in 
appearance  and  in  size,  each  with  its  little  mass  of  pro- 
toplasm about  it,  and  this  protoplasm  appearing  in 
all  the  cells  under  microscopic  examination  very  much 
the  same.  We  cannot  in  this  stage  of  development 
say  of  a  given  cell  that  it  displays  structure  by  which, 


136  AGE,  GROWTH,  AND  DEATH 

'  If  we  saw  the  cell  isolated  under  the  microscope,  we 
could  determine  from  what  part  of  the  young  em- 
bryonic body  it  was  derived.     When  we  see  a  cell 


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Fig.  47.     Three  Sections  through  a  Rabbit  Embryo   of  Seven  and 
One  Half  Days.      For  explanation,  see  Fig.  g,  of  which  this  is  a  repetition. 

from  the  adult  we  can  determine  its  orig-in  in  most 
cases    with    certainty  by  its  microscopic    appearance 


Fig.  48  A.  Entamaba  histolytica^  highly 
MAGNIFIED,  Living  specimen  drawn  from  a 
cover-glass  preparation  from  a  twenty-four-hour 
culture,  by  E.  S.  Kilgore. 


X 


Fig.  48.  B.  Preserved  Specimen 
OF  Entamaba  histolytica,  artificially 
coloured  to  demonstrate  the  large  round 
nucleus.  Same  magnification  as  Fig. 
48  A. — From  a  preparation  loaned  by 
Dr.  Councilman. 

137 


138  AGE,  GROWTH,  AND  DEATH 

alone.  As  development  progresses,  the  simple  con. 
dition  of  the  cells  is  gradually  obliterated,  but  we  find 
another  condition  arising  which  we  call  the  differ- 
entiated one.  Differentiation  is  a  process  which  goes 
on  in  the  body  as  a  whole,  but  of  course  it  is  also  a 
function  of  each  individual  cell. 

We  can  see  something  of  the  process  of  differen- 
tiation if  we  study  the  unicellular  organisms,  those 
creatures,  each  of  which  Is  complete  in  itself,  although 
it  consists  of  but  a  single  cell,  not  of  countless  mil- 
lions of  cells  as  we  do.  The  picture.  Fig.  48,  which 
I  have  chosen  to  throw  upon  the  screen,  is  one  which 
I  think  may  have  an  additional  interest  to  you,  for  it 
is  a  photograph  from  the  living  cell  known  as  the 
parasite  producing  dysentery.  Its  name  is  £n- 
tamceba  histolytica.  Fig.  48  A  is  drawn  from  a  living 
specimen,  which  had  thrown  out  three  short  protuber- 
ances {pseudopodid)  and  had  swallowed  some  foreign 
body,  which  shows  as  a  rounded  dark  mass.  As  the 
nucleus  did  not  show  in  this  specimen.  Fig.  48  B  has 
been  added,  a  drawing  from  an  individual  which  had 
been  preserved  and  artificially  stained,  by  which  double 
treatment,  as  you  see,  the  nucleus  has  been  rendered 
conspicuous.^  Of  course  in  the  living  specimen  the 
nucleus  was  equally  present  although  hidden  by  over- 
lying granules.     Our  Amceba  is  a  unicellular  parasitic 


'  It  gives  me  pleasure  to  thank  Dr.  W.  T.  Councilman  for  the  loan  of  this 
specimen,  obtained  from  the  intestine  of  a  fatal  case  of  amoebic  dysentery.  It 
is  on  Dr.  Councilman's  brilliant  investigations  that  our  knowledge  of  this  disease 
is  based. 


DIFFERENTIA TION  AND  REJUVENA TION      1 3 9 

organism  with  scarcely  any  differentiation  of  its  struc- 
ture. The  next  of  the  slides  shows  us  again  another 
of  these  parasitic  simple  organisms,  namely  Plasmo- 
diziTn  vivax,  the  cause  of  tertian  malarial  fever.  The 
tiny  creature  inhabits  the  blood  corpuscles  of  man  ; 


Fig.  4q.  Tertian  Malarial  Parasite,  Two 
human  blood  corpuscles  alongside  and  drawn 
on  the  same  scale,  by   E.  S.  Kilgore. 

when  it  enters  the  corpuscle  it  is  very  minute, 
scarce  an  eighth  of  the  diameter  of  the  corpuscle  ;  it 
grows  very  rapidly,  feeding  on  and  destroying  the 
corpuscle  and  yet  meanwhile  by  its  own  growth  caus- 
ing the  corpuscle  to  enlarge.  Our  picture.  Fig.  49, 
shows  three  human  red  blood  corpuscles,  two  in  their 
normal  condition,  the  third  (on  the  right)  distended 
by  the  overgrown  parasite,  which  is  heavily  charged 
with  pigmented  granules,  and  almost  completely  fills 
the    corpuscle.     The   nucleus    at   this   stage    of   the 


140 


AGE,  GROWTH,  AND  DEATH 


parasite's  development  is  distributed  as  a  series  of 
small  scattered  granules,  which  cannot  be  demon- 
strated satisfactorily  until  they  have  been  artificially 
coloured.  The  parasite  itself  is  a  small  mass  of  un- 
differentiated protoplasm.  In  another  stage  of  its  life 
cycle  the  Plasmodium  vivax  has  a  distinct  nucleus 
with  only  a  very  little  protoplasm,  and  while  in  that 
stage  it  multiplies  with  that  enormous  rapidity  which 
renders  it  such  a  dangerous  parasite  to  the  human 
race.     I  will  now  show  you  another  picture  of  parasites 


Fig.  50.  Trypanosot?ia  Lewisi,  from  the  rat's 
blood,  with  two  blood  corpuscles  alongside  drawn 
on  the  same  scale,  by  E.  S.  Kilgore. 

— one  form  of  which,  in  a  related  species,  occurs  in 
man.  This  particular  form  is  one  which  occurs  in  the 
rat  and  is  called  the  Trypanosoma.  You  can  see  that 
the  body,  instead  of  being  a  small  and  simple  struc- 
ture,  has  elongated,   acquired    a   peculiar   form,  and 


DIFFERENTIATION  AND  REJUVENATION     141 


here  in  the  interior  are  hghter  and  darker  spots. 
These  do  not  show  very  clearly  in  the  picture,  because 
it  is  from  a  photograph  of  a  living  specimen  under 
the  microscope.  The  lighter  and  darker  spots  corre- 
spond to  the  details  in  the  structure  of  the    organism. 


B 


imiii 


Fig.  51.    Stentor  caruleus;  A,  cut  into  three  pieces;  B,  regeneration  of  the  first  piece; 
C,  of  the  middle  piece;  D,  of  the  posterior  piece.     After  Gruber. 

Here  is  the  tail  of  the  organism,  twisted,  as  you  see, 
and  in  life  capable  of  being  bent.  The  movement  of 
the  animals  in  the  natural  fluid  in  which  they  are 
suspended  is  quite  active.  Alongside  are  some  blood 
corpuscles;  the  figure  is  magnified  about  the  same  as 


142  AGE,  GROWTH,  AND  DEATH 

the  one  of  the  malarial  parasite  which  I  showed  you  a 
few  moments  ago.  The  next  slide,  Fig.  5 1,  exhibits  an 
organism  which  swims  free  in  the  water,  and  is  pretty 
well  shown  in  this  figure.  It  is  called  the  Stentor, 
Fig.  51,  y^.  Here  the  chain  of  beads  represents  the 
nucleus.  The  peculiar  shape  of  the  nucleus  is  a  con- 
stant characteristic  of  this  animal.  Upon  the  surface 
of  the  body  there  are  fine  lines  indicating  superficial 
structure.  At  the  top  there  occurs  what  we  call 
the  mouth.  Over  the  rest  of  this  minute  oro-anism 
there  is  a  thin  cuticle,  but  at  the  mouth  the  cuticle  is 
absent,  and  the  protoplasm  is  naked  or  uncovered  so 
that  food  can  be  taken  in.  There  are  bands  of  hairs 
showing  coarse  and  stiff  in  the  figure  but  capable  of 
movement,  and  with  the  aid  of  its  vibratile  hairs,  or 
cilia,  the  organism  can  swim  about  in  water.  There  is 
another  internal  structure,  the  vacuole,  shown  in  the 
upper  part  of  ^  as  a  circle.  Obviously  in  an  animal 
like  this  we  no  longer  have  simple  protoplasm  alone, 
but  protoplasm  in  part  changed  into  other  things. 
Here  then  within  the  territory  of  a  single  cell  we  have 
differentiation.  If  now  in  these  unicellular  organisms 
we  study  both  the  protoplasm  and  the  nucleus,  we 
learn  that  most  of  these  modifications  which  are  so 
conspicuous  upon  microscopic  observation  are  due  to 
changes  in  the  protoplasm.  It  is  the  protoplasm 
which  acquires  a  new  structure.  In  the  resting  nu- 
cleus, on  the  contrary,  we  find  perhaps  a  change  of 
form,  minor  details  of  arrangement  by  which  one  sort 
of  nucleus,  or  one  stage  of  the  nucleus,  can  be  distin- 


DIFFERENTIATION  AND  REJUVENATION    143 

gulshed  from  another,  but  always  the  nucleus  consists 
of  the  same  fundamental  constants.  There  is  the 
membrane  bounding  it ;  there  is  the  sap  or  juice  in  the 
interior,  and  there  is  the  network  of  living  threads 
stretching  across  it.  Here  and  there  imbedded  in 
and  connected  with  the  network  are  spots  of  a  special 
substance,  which  we  call  chromatin.  These  four 
things  exist  in  the  nuclei  and  are  apparently  always 
present,  and  there  is  usually  not  to  be  seen  in  the 
resting  nucleus  anything  of  change  comparable,  in 
extent  at  least,  with  the  change  which  goes  on  in  the 
protoplasm  —  on  the  other  hand,  the  protoplasm  ac- 
quires items  of  structure  which  were  totally  absent 
from  it  before.  The  nucleus  rearranges  its  parts 
rather  than  changes  them.  This  is  a  very  important 
fact,  and  shows  us,  if  we  confine  our  attention  even  to 
these  little  organisms  only,  that  the  differentiation  of 
the  protoplasm  is  quantitatively  the  more  important 
of  the  two — the  differentiation  of  the  nucleus  the  less 
important. 

We  can  now  turn  from  a  consideration  of  these 
low  organisms  to  the  higher  forms,  among  which  we 
ourselves  of  course  are  counted,  in  which  the  body 
is  formed  by  a  very  considerable  number  of  cells. 
Again  I  should  like  to  take  advantange  of  your  kind- 
ness and  show  you  some  of  the  pictures  we  have 
already  reviewed,  in  order  to  utilise  the  features 
which  they  show  as  illustrations  of  the  fundamental 
principle  that  the  conspicuous  change  is  in  the  proto- 
plasm.     First  we  have  nerve  cells.  Fig.  52.      In  the 


144  AGE^  GROWTH,  AND  DEATH 

two  upper  drawings  are  represented  two  isolated 
nerve  cells,  to  show  their  shape.  They  have  been 
coloured  by  a  special  process  ^  so  dark  that  the  nucleus 
which  they  contain  in  their  interior  is  hidden  from  our 
view ;  it  is  of  course  none  the  less  there.  This  dark 
staining  enables  us  to  trace  out  the  shape  of  these 
cells  very  clearly,  and  you  can  see  that  instead  of 
being  round  and  simple  in  form  they  have  their 
elongated  processes  stretching  out  to  a  very  consid- 
erable distance ;  these  processes  serve  to  catch  up 
from  remote  places  nervous  impulses  and  carry  them 
into  the  body  of  the  cell,  and  thus  assist  in  the  work 
of  nervous  transmission.  The  elongation  of  these 
threads  is,  as  you  see,  adapted,  like  the  elongation  of 
a  Mfire,  to  long-distance  communication.  Here  are 
two  other  figures  which  represent  nerve  cells  treated 
by  a  different  process,'^  and  again  artificially  coloured. 
But  the  colour  in  this  case  has  attacked  certain  spots 
in  the  protoplasm,  consequently  we  see  that  the  pro- 
toplasm around  the  nucleus  in  both  of  these  figures  is 
no  longer  simple  and  uniform,  but  contains  these  de- 
posits of  dark-coloured  material.^  Below  are  three 
other  nerve  cells  ;  the  one  in  the  centre  shows  you 
the  accumulation,  /,  of  pigmented  matter  in  the 
protoplasm  ,  again  an  index  of  change  because  the 
previous  uniformity  has  been  replaced  by  diversity  in 
the  composition  of  the  various  parts  of  the  single  cell. 

1  Carmine. 

^  Nissl's  methylene  blue  method. 

^  The  "  tigroid  markings" — compare  p.  54. 


i 
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, 

Fig.  52.  Various  Kinds  of  Human  Nerve  Cells. — After  Sobotta. 
I.  Two  isolated  multipolar  ganglion  cells  from  the  human  spinal  cord. 
X  ifeo  diams.  2.  Two  multipolar  ganglion  cells  from  the  lumbar  en- 
largement of  the  spinal  cord  of  a  child.  X  480  diams.  3.  Three  cells 
from  a  human  spinal  ganglion,  stained  with  haematoxyline  and  cosine. 
X  420  diams. 

ID  145 


146  AGE,  GROWTH,  AND  DEATH 

Figure  1 1,  p.  50,  shows  us  more  clearly  the  principle  of 
structure  of  a  nerve  cell,  for  there  we  have  the  central 
body  of  the  cell  composed  of  protoplasm  with  its  nu- 
cleus in  the  middle  and  a  s,mall  spot  in  the  centre  of 
the  nucleus,  and  the  long  branching  processes  running 
out  in  all  directions  which  can  take  up  nerve  impulses 
from  other  similar  or  dissimilar  cells,  as  the  case  may 
be,  and  carry  them  to  the  central  body.  To  carry  the 
message  out  there  is  typically  but  one  process,  which 
is  different  in  appearance  from  the  other  processes 
which  carry  the  impulses  in.  The  latter  are  branch- 
ing and  are  therefore  called  the  tree-like  or  dendritic 
processes.  Here  is  a  single  process  (Fig.  11,  Ax) 
like  a  long  thread  to  carry  the  impulses  away,  and 
which  is  called  the  axon  of  the  nerve  cell.  In  this 
case  the  modification  of  the  shape  of  the  cell  has 
adapted  it  to  the  better  performance  of  its  functions. 
Notice  also  in  these  cells  the  enormous  increase  in 
the  amount  of  protoplasm  as  compared  with  the  nu- 
cleus. In  the  young  cell  of  the  rabbit  germ,  of  which 
I  showed  you  several  illustrations  a  few  moments  ago, 
we  had  very  little  protoplasm  for  each  nucleus,  but 
here  the  protoplasm  has  many,  many  times  the  volume 
of  the  nucleus,  and  this  is  a  relatively  old  cell.^ 

Next  let  us  look  again  at  the  figure  of  the  striated 

'  The  nerve  fibres  of  vertebrates  are  usually  each  surrounded  by  a  protective 
covering  of  cells,  making  a  sheath.  Kolliker  pointed  out  in  1886  that  the 
sheath  cells  are  very  small  in  young  embryonic  stages  and  that  their  size  increases 
with  age,  owing  not  to  the  growth  of  the  nuclei,  but  to  the  growth  of  the  cell 
body,  including  the  myelin,  the  special  substance  which  characterises  the  dif- 
ferentiation of  these  cells.  See  "  llistologische  Studien  an  Batrachier  Larven," 
Zeitschr .  fiir  wiss.  Zoologie,  xliii.,  p.  1. 


DIFFERENTIATION  AND  REJUVENATION    147 


muscle  fibre,  Fig.  53,  which  you  may  recall  from  the 
second  lecture,  so  that  it  will  suf^ce  if  your  atten- 
tion is  again  directed  to  the  oval 
nuclei,  and  to  the  lines  stretching 
crosswise  on  the  muscle  giving  it 
a  "  striated  "  appearance.  You  re- 
member, doubtless,  that  such  fi- 
bres are  the  ones  which  enable  us 
to  make  voluntary  motions.  Orig- 
inally each  fibre  was  a  set  of  cells, 
and  the  cells  had  some  protoplasm, 
but,  gradually,  as  development  pro- 
gressed, there  appeared  in  them 
longitudinal  fibrils  different  from 
the  protoplasm,  and  the  fibrils 
also  created  ultimately  the  appear- 
ance  of   cross   lines   on   the    fibre. 

T       •         1       i^i     M         1  •    1  r  1  ^^°-  53-      Part  OF  A 

It   IS   the  hbrils  which  perform  the    human  muscle  fibre. 
muscular   contractions.      It  is  not 
the  original  unmodified  protoplasm,  but  the  modified 
or  differentiated  muscular  cell  which  is  capable  of  vol- 
untary contraction. 

The  next  picture,  Fig.  54,  shows  us  clearly  and 
strikingly  how  much  the  differentiation  may  vary. 
We  have  here  another  type  of  differentiation.  These 
are  gland  cells  ;  we  can  see  here,  as  I  pointed  out  to 
you  before,  the  material  in  the  form  of  granules,  which 
is  to  produce  the  secretion  from  these  gland  cells. 
This  is  an  orbital  gland,  and  here  are  the  cells,  which 
are  very  much  smaller  because  they  have  discharged 


148 


AGE,  GROWTH,  AND  DEATH 


their  secretion  and  are  very  conspicuous  on  account 
of  their  dark  colour.  Three  typical  cells  are  repre- 
sented separately  (Fig.  55).     The  first  shows  us  a  cell 

full  of  the  material  which  is  to 
be  discharged  and  is  to  form  a 
part  of  the  salivary  secretion. 
The  second  is  a  cell  which  has 
partly  lost  its  accumulated 
material,  and  the  third  is  one 
which  has  discharged  it  almost 
completely,  so  that  it  has  be- 
come very  much  reduced  in 
size.  We  learn  from  these  ob- 
servations and  others  similar 
that  the  size  of  cells  may  vary 
also  according  to  their  func- 
tional  condition.  Let  me  refer 
back  to  an  earlier  picture 
(Fig.  16J  representing  a  section 
of  the  so-called  salivary  gland  of  the  intestine,  better 
termed  the  pancreas.  Here  we 
can  see  for  each  of  these  cells  a 
nucleus  and  a  body  divided  into 
two  parts,  a  darker  portion 
around  the  nucleus  and  a  lighter 
part  with  little  granules  in  it, 
which  represents  the  accumu- 
lation of  material  which  is  to 
form  the  secretion.  When  the 
cells  have  discharged    their  secretion,   they,   like   the 


Fig.  54.  Section  from  an 
Orbital  Gland  of  a  Dog  — 
After  Lavdowsky. 


Fig.  55.  Diagram  of 
Three  Cells  of  a  Sal- 
ivary Gland,  to  Illus- 
trate THE  Change  Re- 
sulting from  the  Dis- 
charge of  the  Secretion. 


DIFFERENTIATION  AND  REJUVENATION    149 

cells  in  the  salivary  gland,  are  found  to  have  dimin- 
ished in  size  and  become  very  much  smaller  indeed 
than  they  were  in  their  earlier  state  when  charged 
with  the  zymogen  destined  to  be  given  out.  In  this 
case  also  we  have  an  illustration  of  a  functional 
variation  in  the  size  of  the  cells.  This  ends  the  series 
of  pictures  which  I  wanted  especially  to  show  to  you 
as  illustratinor  the  changes  of  the  cells  as  their  differ- 
entiation  progresses.  We  can  see  in  the  bodies  of  the 
cells  the  changes  which  have  occurred. 

Here  is  a  picture  (Fig.  56)  which  teaches  us  one 
thing  more  about  these  cells.  Notice  the  scattered 
nuclei,  each  surrounded  by  protoplasm,  completing 
the  cell.  The  protoplasm  of  each  of  these  cells  is 
connected  across  with  the  protoplasm  coming  from 
another,  so  that  the  whole  set  of  cells  forms  an  ir- 
regular protoplasmic  network.  Now  in  the  spaces 
between  these  cells  are  fine  lines.  These  represent 
delicate  structures  which  we  call  connective  tissue 
fibrils,  which  have  a  mechanical  function.  By  their 
tensile  strength,  their  power  to  resist  a  pull,  they  give 
a  certain  supporting  power  to  the  tissues.  Our  pic- 
ture represents  one  of  the  tissues  which  support  and 
connect  other  portions  of  the  body.  Now  the  fibrils 
apparently  lie  entirely  disconnected  from  the  cells, 
but  a  more  careful  study  of  the  history  of  the  con- 
nective tissue  has  revealed  the  very  interesting  and 
instructive  fact  that  the  fibrils,  now  separate  from  the 
cells,  arose  by  a  metamorphosis  of  the  protoplasm  of 
the  cells — that  they  are  first  formed  out  of  some  of 


15° 


AGE,  GROWTH,  AND  DEATH 


the  protoplasm  of  these  cells,  then  split  off  from  them, 
and  come  to  lie  in  the  intercellular  regions,  so  that 
here  we  have  another  type  of  cell  differentiation 
brought  to  our  notice,  one  in  which  the  product  is 
separated  from  the  parent  body  to  which  it  owes  its 
origin.  Now  you  will  perceive  immediately,  if  you 
recall  the  series  of  pictures  which  have  just  passed 


■^ /f^^^J^^^^. 


>^A  ^-'rT,    \^w  '<    V'd 


y  ^,.«=/(^^f'   '.vy^;|^ijj  ^.'■^■^/F//'''     rV 
.,  1/   If  :^<y  'I  ■■..^    W^'t^^'^m 


J 


w  ^■. 


Fig.  56.     Embryonic  Syncytium  from  the  Umbilical   Cord  of  Man  ; 
c,  c,  cells  ;  F,  fibrils. 

before  us,  very  great  differences  in  the  types  of  differ- 
entiation which  occur  in  the  body,  and  had  we  time 
we  might  find  a  very  much  larger  range  easily  to  be 
represented  before  us. 

In  the  second  lecture  a  picture  was  projected  upon 


DIFFERENTIATION  AND  REJUVENATION     151 

the  screen  (Fig.  22)  which  showed  motor  nerve  cells 
of  various  animals.  You  will  recall  that  I  directed 
your  attention  to  the  fact  that  the  largest  animal,  the 
elephant,  has  the  largest  cells,  and  the  smallest  ani- 
mals, the  rat,  the  mouse,  and  the  little  bat,  have  the 
smallest  ones.  But  let  me  point  out  to  you  that  the 
question  of  the  size  of  cells  is  exceeding  complex,  and 
that  in  studying  it  we  have  to  exercise  a  great  deal  of 
caution.  We  know  that,  with  the  exception  of  the 
nerve  cells  and  to  a  minor  degree  with  the  exception 
of  the  muscle  fibres,  the  cells  in  each  animal  are  more 
or  less  uniform  constants  in  size.  The  cells  of  dif- 
ferent organs  differ  somewhat  from  one  another.  A 
single  organ  may  have  in  its  different  parts  typical 
sizes  of  cells,  but  each  of  these  kinds  of  cells  has  its 
definite  dimensions.  When  one  animal  is  larger  than 
another,  it  has  more  cells.  Now  it  is  a  very  important 
fact  for  us  that  animals  have  a  more  or  less  constant 
size  of  their  cells.  They  do  not  differ  from  one  an- 
other by  a  difference  in  the  size  of  their  cells ;  the 
bigness  of  an  animal  does  not  depend  upon  the  size, 
but  upon  the  number,  of  its  cells.  We  can,  therefore, 
in  studying  the  changes  of  size,  to  which  I  shall  next 
direct  your  attention,  omit  altogether  these  details, 
and  speak  of  the  cells  in  a  general  way  safely  as  hav- 
ing a  certain  uniform  or  standard  size.  This  will  save 
us  a  great  deal  of  time,  for  we  learn,  as  we  study  cells, 
that  their  size  increases  with  the  age  of  the  animal. 
Since  the  animal,  when  it  is  young,  has  cells  with  a 
small  amount  of  protoplasm,  the  increase  of  proto- 


152  AGE,  GROWTH,  AND  DEATH 

plasm  with  age  is  an  absolutely  necessary  corollary  of 
the  discovery  that  differentiation  is  mainly  a  function 
of  the  protoplasm.  If  there  is  to  be  a  large  degree  of 
differentiation  it  is  necessary  that  the  quantity  of  pro- 
toplasm in  the  single  cells  should  be  increased,  so 
that  there  may  be  the  raw  material  on  hand  out  of 
which  the  differentiated  product  can  be  manufactured. 
If  there  is  not  such  a  preliminary  increase  of  the  pro- 
toplasm, then  the  differentiation  cannot  occur.  In 
order  that  the  perfection  of  the  adult  structure  should 
be  attained,  it  is  necessary  that  the  mere  undifferen- 
tiated cells,  each  with  a  small  body  of  protoplasm, 
should  acquire  first  an  increased  amount  of  proto- 
plasm, and  that  then  from  the  increased  protoplasm 
should  be  taken  the  material  to  result  in  differenti- 
ation, in  specialisation. 

An  undifferentiated  cell  performs  all  the  fundamen- 
tal functions  of  life.  An  amoeba,  or  any  unicellular 
organism  such  as  I  have  presented  to  you  upon  the 
screen,  does  everything  which  is  indispensable  to  life. 
It  takes  food ;  it  forms  secretions  and  excretions ;  its 
activity  depends  upon  chemical  alterations  going  on  in 
the  food  in  the  interior  of  its  body  ;  it  is  capable  of 
sensation  and  of  locomotion.  It  is  probable  that  every 
living  cell  has  all  of  these  fundamental  properties  of 
protoplasm.  When  a  cell  becomes  differentiated, 
however,  though  it  does  not  necessarily  give  up  any 
of  its  vital  properties,  it  becomes  different  from  other 
cells  because  one  of  its  properties  is  made  conspic- 
uous, and  in  order  to  acquire   that  conspicuousness. 


DIFFERENTIATION  AND  REJUVENATION     153 

that  excess  of  development  of  one  function  of  the  cell, 
a  modification  in  the  structure  is  necessary.  The  ap- 
paratus in  the  interior  of  a  cell  to  produce  the  ex- 
aggeration of  the  function  must  be  developed,  so  that 


Fig.  57. 


Amceba  PROTEUS,  photograph  of  a  specimen    prepared  by 
Prof.    G.  N.  Caikins. 


to  effect  the  complex  physiological  machinery  of  the 
adult  body,  this  differentiation,  of  which  I  have  so 
often  spoken,  is  indispensable.  A  nerve  cell  carries 
on  all  the  vital  functions,  but  it  has  in  addition  a  special 


154  AGE,  GROWTH,  AND  DEATH 

series  of  modifications  of  its  protoplasm  which  enable 
it  to  accomplish  the  transmission  of  the  nervous  im- 
pulses with  greater  efficiency  than  ordinary  protoplasm 
can  do,  probably  at  a  higher  speed  and  with  a  more 
perfect  adjustment  of  communication  between  the 
various  parts  of  the  body  than  is  possible  with  any 
machinery  of  pure  protoplasm.  So,  too,  the  glands 
have  cells  which  are  especially  capable  of  elaborating 
chemical  substances  which,  when  they  are  poured  out, 
accomplish  the  work  of  digestion,  for  instance.  But 
these  cells  are  likewise  alive  in  all  their  parts.  They 
have  all  the  fundamental  vital  properties,  but  there  is 
a  tremendous  exaggeration  of  one  faculty,  and  that 
involves  an  alteration  so  great  in  the  protoplasm  that 
we  can  see  it  with  the  microscope  ;  the  microscope 
affords  us  a  perfect  visible  demonstration  of  differen- 
tiation, which  we  can  correlate  with  the  function. 

The  primary  object,  therefore,  of  all  differentiation 
is  physiological.  The  higher  organism,  with  its  com- 
plex physiological  relations,  is  something  really  higher 
in  structure  than  the  lower  organism.  The  term 
"higher"  in  biology  implies  a  much  more  complex 
interrelation  of  the  parts,  a  much  more  complex  re- 
lation of  the  organism  to  the  outside  world  ;  and  above 
all  it  implies  in  the  highest  animals  a  complex  intelli- 
gence of  which  only  a  rudimentary  prophecy  exists  in 
the  lowest  forms  of  life,  possibly  scarcely  more  than  a 
mere  sensation.  We  owe  then  to  differentiation  our 
faculties,  which  we  prize.  It  is  the  result  of  differ- 
entiation that  I  am  able  to  address  you  and  present 


DIFFERENTIATION  AND  REJUVENATION     155 

before  you  the  thoughts  which  have  been  accumulated 
as  the  result  of  the  studies  of  many  years.  It  is  a  result 
of  differentiation  that  you  have  such  parts  that  you  not 
only  hear  the  actual  sound  of  my  voice,  but  interpret — 
at  least  I  hope  so — the  meaning  of  my  words  and  can 
understand  the  ideas  which  I  am  endeavouring  to  pre- 
sent to  you.  If  you  carry  away  something  from  these 
lectures,  and  recall  it  at  some  future  time,  that  also 
will  be  a  result  of  the  differentiation  of  structure ;  for 
every  one  of  you  started  as  a  minute  germ,  consisting 
of  protoplasm  with  a  nucleus,  and  entirely  without 
any  differentiation ;  and  by  a  process  so  intricate  that 
the  mystery  of  it  escapes  entirely  all  our  powers  of 
analysis,  those  parts  which  you  have  have  been  slowly 
and  secretly  fashioned.  We  have  approached  one  of  the 
fundamental  problems  of  existence.  When  we  talk  of 
dfferentiation,  we  talk  of  the  endowments  which  bring 
us  into  relation  with  the  external  world — into  rela- 
tions with  our  kind,  and  which  make  our  internal  life 
so  complex,  a  complexity  which  in  itself  is  a  great 
problem.  We  touch  here  the  fundamental  mysteries 
of  existence  ;  we  are  hovering  upon  the  outskirts  of 
our  human  conceptions.  We  are  not  yet  able  to  press 
beyond.  But  perhaps  the  time  may  come  when  the 
limit  to  which  I  can  now  bring  you  will  be  moved 
farther  back,  and  some  of  the  things  which  are  at  the 
present  time  utterly  mysterious  and  incomprehensible 
to  us  will  be  comprehended  and  be  explicable  to  you. 
The  increase  of  the  protoplasm  is  then,  as  we  have 
clearly    seen   from  the    pictures,   the   mark   both  of 


156  AGE,  GROWTH,  AND  DEATH 

advancing  organisation  and  of  advancing  age.  It  is 
certainly  somewhat  paradoxical  to  assert  that  the  in- 
crease of  the  protoplasm  is  a  sign  of  old  age,  a  sign  of 
senescence,  since  protoplasm  is  the  physical  basis  of 
life.  It  undoubtedly  is  such,  and  we  should  hardly 
anticipate  that  its  increase  would  have  a  deleterious 
effect.  But  such  is,  it  seems  to  me,  clearly  the  case. 
But  it  is  not  merely,  of  course,  a  question  of  the  in- 
crease of.  protoplasm  which  we  must  bear  in  mind  in 
estimating  the  cause  and  effect,  but  also  the  question 
of  differentiation,  in  consequence  of  which  protoplasm 
becomes  something  else  and  different  from  what  it 
was  before.  This  alteration,  then,  together  with  the 
increase  of  the  protoplasm,  is  the  change  which  in  all 
parts  of  the  body  marks  the  passage  from  youth  to 
old  age. 

It  seems  to  me  not  going  at  all  too  far  to  say  that 
the  increase  of  protoplasm  is  a  fundamental  pheno- 
menon. I  wish  to  give  you  a  more  precise  notion  of 
this  increase  ;  and  I  am  glad  to  be  able  to  do  so  in 
consequence  of  a  research  carried  on  by  Professor 
Eycleshymer  in  my  laboratory  and  completed  by  him 
afterwards  in  his  own  laboratory  at  the  University  of 
St.  Louis. ^  He  studied  the  development  of  the  muscle 
fibres  in  the  great  salamander,  known  scientifically  by 
the  name  of  Necturus.  These  muscle  fibres  are  some- 
what cylindrical  in  shape.   Their  ends  can  be  accurately 

'  A.  C.  Eycleshymer,  "The  Cytoplasmic  and  Nuclear  Changes  in  the  Striated 
Muscle  Cell  of  Necturus  "  American  Journal  of  Anato?ny,  iii.,  2S5-310.  This 
paper  is  of  exceptional  importance  as  a  contribution  to  our  knowledge  of  the  life- 
history  of  cells, 


DIFFERENTIA  TION  AND  RE  J  U  VENA  TION     1 5  7 

determined  so  that  the  precise  length  of  a  fibre  can 
be  measured,  and  its  diameter  also.  Hence  the  total 
volume  of  a  fibre  may  be  calculated.  It  is  possible 
also  to  measure  the  nuclei  and  to  count  the  number 
of  nuclei  in  a  fibre.  Thus  by  measuring  the  diameter 
and  length  of  the  fibre,  and  then  estimating  the  number 
and  the  diameters  of  the  nuclei,  the  author  was  able  to 
calculate  the  relative  proportions  of  the  nuclei  and  the 
protoplasm.  As  a  matter  of  fact,  the  nuclei  remain 
nearly  constant  in  volume,  not  really  quite  so,  but 
sufficiently  constant  to  serve  as  a  basis  of  measurement. 
Dr.  Eycleshymer  found  that  when  a  Necturits  had  a 
length  of  eight  millimetres,  it  possessed,  for  each  nu- 
cleus in  its  muscle  fibre,  2737  units  of  protoplasm,  but 
when  it  was  seventeen  millimetres,  it  possessed  for  each 
nucleus,  4318  units  per  nucleus;  at  twenty-six  milli- 
metres, 8473  units  ;  and  in  the  adult,  which  measures 
approximately  230  millimetres,  it  has  22,379  units  per 
nucleus.  In  other  words,  as  a  salamander  passes  from 
the  eight-millimetre  condition,  when  the  development 
of  its  muscle  fibers  is  just  fairly  begun,  up  to  the  adult 
state,  when  the  differentiation  of  the  muscle  fibres  has 
been  completed,  it  increases  the  proportion  of  pro- 
toplasmic substance  and  protoplasmic  derivatives  from 
2700  to  22,300  per  nucleus.  I  give  round  numbers. 
The  increase  is  approximately  eightfold.  There  is  in 
the  adult  in  the  muscle  fibre  eight  times  as  much 
protoplasmic  substance  in  proportion  to  the  nucleus 
as  there  was  at  the  start  of  development  when  the 
muscle  fiber  could  first  be  clearly  recognised  as  such. 


158  AGE,  GROWTH,  AND  DEATH 

This  is  an  accurate  measure  and  gives  us  a  good  idea 
of  the  general  law  of  protoplasmic  increase.  It  is 
the  only  instance,  I  yet  know  of,  in  which  we  have  an 
accurate  measure  and  can  give  quantitative  values, 
though  we  do  know  that  there  is  a  more  or  less  similar 
increase  occurring  in  perhaps  every  tissue  of  the  body. 

While  the  increase  of  the  protoplasm  is  going  on, 
we  find  that  there  is  an  advance  in  the  structure,  in 
the  differentiation.  Now  you  may  recall  what  I  have 
mentioned,  earlier  in  this  lecture,  the  further  funda- 
mental fact  that  the  loss  in  the  rate  of  gfrowth  is 
greatest  in  the  young,  least  in  the  old,  and  that  as 
we  go  back  from  old  age  towards  youth,  and  then 
into  the  embryonic  period,  we  find  an  ever-increasing 
power  of  growth,  but  that  it  is  during  the  embryonic 
period  that  the  loss  of  the  power  of  growth  is  greatest. 
It  is  to  the  embryonic  period,  therefore,  that  I  have 
turned  in  order  to  ascertain  whether  the  rate  of 
differentiation  shows  a  similar  relation  in  the  de- 
velopment of  the  organism. 

We  have  a  large  series  of  microscopic  preparations 
of  rabbit  embryos  in  the  embryological  laboratory 
of  the  Harvard  Medical  School.  Utilising  these,  I 
found  that  at  seven  or  eight  days  of  development 
there  is  scarcely  a  trace  of  differentiation.  The  cells 
are  in  the  condition  of  those  which  I  showed  to  you 
earlier  in  the  lecture  upon  the  screen  (Fig  47).  At 
sixteen  and  a  half  days,  a  stage  of  development  of 
which  I  have  some  good  preparations,  I  found  that 
a  great  deal  had  been  accomplished.      At  seven  days 


DIFFERENTIATION  AND  REJUVENATION     159 

there  was  no  brain,  there  was  no  spinal  cord,  nothing 
that  could  possibly  be  called  skin  or  muscle,  or  intes- 
tine or  heart.  None  of  those  things  were  yet  produced. 
But  at  sixteen  and  one  half  days — in  other  words,  after 
a  very  brief  period  indeed — only  nine  days  of  the  whole 
life  of  the  animal — there  have  arisen  from  this  inchoate 
beginning  all  the  principal  organs  of  the  body.  The 
brain  is  there,  divided  up  into  its  principal  funda- 
mental parts;  the  spinal  cord  has  its  nerves  in  con- 
nection with  the  various  parts  of  the  body ;  there  is  a 
trace  of  the  skeletal  element ;  the  stomach,  the  liver, 
the  pancreas,  the  intestines,  are  all  present  and  well 
defined;  the  heart  is  a  large  and  beating  organ,  amply 
supplied  with  blood,  connected  with  vessels,  which 
carry  out  and  bring  back  the  blood  and  are  all  far 
along  in  their  development.  Equally  instructive  is  the 
microscopic  examination,  for  we  can  see  that  the  cells 
themselves  have  been  changed.  Not  only  have  the 
great  organs  been  mapped  out  in  this  brief  period,  but 
the  cells  which  belongr  to  them  have  for  each  oro-an  ac- 
quired  a  characteristic  quality.  In  the  brain  there 
are  nerve  cells  with  their  long  processes  to  carry  the 
impulse  in  ;  the  single  process  (axon)  to  carry  it  out. 
The  glands  in  the  stomach  have  the  cells  which  are 
to  build  them  already  there.  The  muscles  which  are 
to  move  the  stomach  are  beginning  to  appear  as  cells 
of  a  special  form.  Nerve  fibres  extend  down  into  the 
gastric  region  and  to  the  various  distant  organs  of 
the  body.  Muscle  fibres  can  be  recognised  along  the 
back  and  in  the  limbs,  and  so  in  every  part  of  the  body 


i6o  AGE,  GROWTH,  AND  DEATH 

we  can  detect  cells  already  far  advanced  in  their  de- 
velopment. It  is  not  certainly  too  much  to  say  that 
in  the  brief  period  of  these  nine  days  fully  as  much 
differentiation  has  been  accomplished  as  is  accom- 
plished during  the  entire  remainder  of  the  life  of  the 
animal.  We  do  not,  at  present  at  least,  possess  any 
method  of  measuringf  differentiation  which  enables 
us  to  state  it  numerically,  but  no  one  who  is  familiar 
with  these  matters  and  observes  the  structure,  as  I 
have  myself  observed  it,  would  hesitate  for  a  moment, 
it  seems  to  me,  to  decide  that  my  assertion  is  perfectly 
within  the  bounds  of  truth,  that  within  a  period  of  nine 
days,  half  of  the  entire  differentiation  which  is  to  oc- 
cur in  the  whole  life  of  the  rabbit  has  been  completed. 
We  must  from  this  conclude  that  the  rate  of  differ- 
entiation is  very  rapid  at  first  and  afterwards  declines, 
and  as  we  compare  the  different  stages  of  develop- 
ment we  can  see  readily  that  this  is  the  case.  The 
progress  in  the  additional  development  in  the  rabbit 
from  sixteen  and  one  half  days  up  to  the  time  of  its 
birth  is  far  greater  than  the  progress  which  occurs 
after  birth.  We  find,  moreover,  in  the  study  of  these 
embryonic  conditions,  some  instructive  things,  for  in 
certain  parts  of  the  body  the  process  of  differentiation 
hurries  along,  and  as  the  cells  are  differentiated  their 
power  of  growth,  to  a  large  extent,  is  stopped.  On 
the  other  hand,  there  are  various  provisions  in  the 
developing  animal  for  keeping  back  certain  cells,  al- 
lowing them  to  remain  in  the  young  state.  Such  cells 
may  afterward  differentiate. 


DIFFERENTIATION  AND  REJUVENATION     i6i 

From  all  that  has  been  said  it  seems  to  me  legiti- 
mate to  conclude  that  there  is  an  intimate  correlation 
between  the  rate  of  differentiation  and  the  rate  of 
growth.  I  am  inclined  to  go  the  one  step  farther, 
and  bring  them  into  the  relation  of  cause  and  effect; 
and  I  present  to  you  as  the  main  general  conclusion  of 
this  first  part  of  our  series  of  lectures,  the  conception 
that  the  growth  and  differentiation  of  the  protoplasjn 
are  the  cause  of  the  loss  of  the  power  of  growth} 

Now  if  cells  become  old  as  their  protoplasm  in- 
creases and  becomes  differentiated,  we  should  expect 
to  find  that  there  would  be  a  provision  for  the  pro- 
duction of  young  cells.  It  is  rather  mortifying  to 
reflect  that  the  simple  conception  which  I  have  now 
to  express  to  you,  although  it  lay  close  at  hand,  failed 
to  combine  itself  in  my  mind  for  many  years  with  the 
conception  of  the  process  of  senescence  as  I  have  just 
described  it  to  you.  It  is  somewhat,  it  seems  to  me,  like 
two  acquaintances  of  mine  who  lived  long  side  by  side, 
seeing  one  another  frequently  until  they  were  fairly 
past  the  period  of  youth,  when  their  attachment 
became  very  close  and  by  a  sacrament  they  were 
permanently  joined  together.  So  in  the  minds  of 
men  often  two  ideas  lie  side  by  side  which  ought  to 
be  married  to  one  another,  and  there  is  no  one  ready 
so  dull  is  the  owner  of  the  mind,  to  pronounce  the 
sacramental  words  which  shall  join  them,  and  the  rite 

^  The  hypothesis  that  the  increase  of  protoplasm  is  the  cause  of  old  age  was 
originally  put  forward  in  1890(0.  S.  Minot,  "  On  Certain  Phenomena  of  Grow- 
ing Old,"  P)-oc.  American  Assoc.  Adv.  Science,  xxix.,  Address  of  the  Vice- 
President,  Section  F). 


l62 


AGE,  GROWTH,  AND  DEATH 


long  remains  unperformed,  and  when  at  last  such 
neighbour  ideas,  which  naturally  should  be  united  in 
close  companionship,  are  brought  together  and  made, 
as  it  were,  into  one,  we  are  astonished  that  the  in- 
evitableness  of  the  union  had  not  obtained  our  notice 
before,  it  is  so  very  obvious.  And  so  in  regard  to  the 
conception  of  what  constitutes  the  restoration  of  the 
young  state,  I  have  only  this  excuse  to  offer,  which  I 
have  indicated  to  you,  that  even  the  natural  thought 


Fig.  58.     Tarsius  spectabile.     Sections  of  Three  Ova  in  very  Early  Stages. 
I,  before  cleavage;  2,  cleavage  into  four  cells;  3,  multicellular  stage. 

fails  to  occur  to  us.     We  are  very  dull  even  if  we  are 
scientific. 

The  pictures  now  before  you  represent  certain  early 
stages  in  the  progress  of  development  of  a  mammal 
by  the  name  of  Tarsius,  a  creature  related  to  the  le- 
murs. The  various  figures  illustrate  the  multiplica- 
tion of  the  cells.  That  which  I  wish  to  call  your 
attention  to  can  be  well  demonstrated  by  the  com- 
parison of  the  first  figure,  in  which  there  is  a  single 


DIFFERENTIATION  AND  REJUVENATION     163 

nucleus,  with  the  figure  on  the  right  having  a  number 
of  nuclei.  Both  figures  represent  the  very  earliest 
stages  of  development  and  show  the  full  size  of  the 
whole  germ,  which  is  about  the  same  in  the  two  stages. 
The  total  amount  of  living  material  has  not  changed 
essentially,  but  evidently  there  has  occurred  a  marked 
increase  of  the  nuclear  substance^i_The  nuclei  have 
in  the  right-hand  figure  multiplied  in  number  and 
their  combined  volume  is  much  o-reater  than  the  total 
volume  of  the  single  nucleus  in  the  left-hand  figure^ 

The  increase  in  the  amount  of  nuclear  material  dur- 
inor  the  seg-mentation  of  the  ovum  occurs  in  all  classes 
of  animals  and  has  been  recorded  by  hundreds  of 
observers.  It  has  hitherto  attracted  very  little  at- 
tention and  despite  the  constancy  and  universality  of 
the  phenomenon  no  special  significance  has  been  at- 
tributed to  it,  I  emphasised  the  constancy  of  the 
phenomenon  in  1890  in  an  address  delivered  before 
the  American  Association  for  the  Advancement  of 
Science.  ^  Since  then  Richard  Hertwie  has  been  the 
only  author  to  lay  special  stress  on  the  fact,  but  he 
fails  to  make  the  interpretation,  which  I  shall  offer 
you  in  a  few  moments. 

We  can  get  a  further  notion  of  the  nuclear  increase 
by  studying  the  very  early  development  of  a  salaman- 
der (Fig.  59).  Here  upon  the  screen  is  the  e.gg  of  a 
salamander,  No.  i.  It  represents  really  but  a  single 
cell.  It  then  divides  into  two  cells  :  each  of  those 
cells  has  a  nucleus  which  we  cannot  see  because  these 

1  Froc.  A.  A.  A.  S.,  xxxix. 


164 


AGE,  GROWTH,  AND  DEATH 


pictures  are  taken  from  the  living  Qgg,  and  the  living 
egg  is  not  transparent.     Here  (No.  4),  it  is  dividing 


Fig.  59.     Amblystomnm  piinciatwii.     Progressive  Segmentation  of  the  Ovum. 
I,  unsegmented  ovum;  9,  advanced  segmentation. — After  A.  C.  Eycleshymer. 

into  four,  here  (No.  5),  the  upper  portion  of  the  four 
cells  has  been  split  off,  and  we  have  seven  cells  showing 


DIFFERENTIATION  AND  REJUVENATION    165 

In  the  figure,  and  an  eighth  on  the  back.  Here  (No.  9) 
the  number  of  cells  has  increased  very  much.  As  you 
view  these  figures  you  will  notice  that  they  look  very 
much  indeed  like  oranges  divided  into  segments.  It 
seems,  in  fact,  as  if  this  &gg,  which  was  spherical  in 
form,  were  being  divided  up  into  a  certain  number  of 
segments.  The  process  was  first  observed  in  the  eggs 
of  some  of  the  amphibia  (frogs,  toads  and  salaman- 
ders), and  it  was  therefore  called  segmentation,  because 
it  was  not  known  at  that  time  what  the  process  really 
meant.  We  have  then  before  us  an  ovum  and  a  series 
of  stages  of  the  segmentation  of  the  ovum,  and  the 
result  of  that  segmentation  is  to  produce  an  ever- 
increasing  number  of  cells  which,  in  the  last  of  the 
figures  upon  the  screen,  have  become  so  numerous 
that  we  are  no  longer  able  to  count  them  readily. 
Every  one  of  these  cells  has  its  own  nucleus.  When 
the  process  of  segmentation  is  complete  and  reaches 
its  final  limit,  we  then  see,  if  we  examine  that  stage 
of  development,  cells  of  the  young  type,  such  as  I~ 
have  described  to  you,  in  which  there  is  a  nucleus 
with  a  small  amount  of  protoplasm  about  each  nucleus. 
It  seems  to  me,  therefore, — and  this  is  a  new  interpre- 
tation which  I  present  to  you, — that  the  process  of 
segmentation  of  the  ovum,  with  which  the  develop- 
ment of  all  the  animals  of  the  higher  type  invariably 
begins,  is  really  the  process  of  producing  young  cells. 
It  is  the  process  of  rejuvenation.  There  is  not  any 
considerable  growth  of  the  living  protoplasmic  ma- 
terial of  these  eggs,  and  at  the  final  stage  the  total 


1 66  AGE,  GROWTH,  AND  DEATH 

volume  of  the  egg  is  scarcely  bigger  than  before  ;  and 
such  increased  volume  as  has  occurred  has  been  due 
to  the  absorption  of  some  of  the  surrounding  water. 
In  many  animals  not  even  this  increase  by  the 
absorption  of  water  takes  place.  During  the  segmen- 
tation of  the  ovum  the  condition  of  things  has  been 
reversed  so  far  as  the  proportions  of  nucleus  and  pro- 
toplasm are  concerned.  We  have  nucleus  produced, 
so  to  speak,  to  excess.  The  nuclear  substance  is  in- 
creased during  this  first  phase  of  development.  Hence 
our  conclusion  :  Rejuvenation  is  accomplished  chiefly 
by  the  segmeiitation  of  the  ovum. 

Naturally,  as  we  embryologists  looked  upon  these 
things  in  earlier  days  and  thought  of  the  progress  of 
development,  we  conceived  of  the  earlier  stage  as 
younger,  and  of  the  ovum  as  being  the  youngest 
stage  of  all,  a  conception  which  in  terms  of  time  is 
obviously  correct,  but  as  regards  the  nature  of  the 
development,  it  seems  to  me  clearly,  is  not  correct. 
The  ovum  is  a  cell  derived  from  the  parent  body, 
fertilised  by  the  male  element,  and  presenting  the 
old  state  to  us,  the  state  in  which  there  is  an  excessive 
amount  of  protoplasm  in  proportion  to  the  nucleus ; 
and  in  order  to  get  anything  which  is  young,  a  process 
of  rejuvenation  is  necessary,  and  that  rejuvenation  is 
the  first  thing  to  be  done  in  development.  The  nuclei 
multiply ;  they  multiply  at  the  expense  of  the  protoplasm. 
They  take  food  from  the  material  which  is  stored  up  in 
the  ovum,  nourish  themselves  by  it,  grow  and  multiply 
until  they  become  the  dominant  part  in  the  structure. 


DIFFERENTIATION  AND  REJUVENATION    167 

To  be  exact,  it  must  be  added  that  the  relative  in- 
crease of  the  nuclei  may  be  prolonged  beyond  the 
period  of  segmentation  as  commonly  defined.  Then 
begins  the  other  change  ;  the  protoplasm  slowly  pro- 
ceeds to  grow,  and  as  it  grows,  differentiation  follows, 
and  so  the  cycle  is  completed.  Whether  other  na- 
turalists will  be  Inclined  to  accept  this  conception  that 
the  process  of  the  segmentation  of  the  ovum  is  that 
which  we  must  call  rejuvenation  or  not,  I  cannot  say, 
for  the  matter  has  as  yet  been  very  little  discussed, 
but  you  must  admit  that  the  conception  hangs  as  a 
theory  well  together  with  the  main  facts  of  senescence 
as  now  known  to  us.  We  have  first  an  explanation 
of  the  process  of  the  production  of  the  young  material, 
and  next  out  of  that  young  material  the  fashioning  of 
the  embryo.  The  cycle  of  life  has  two  phases,  an 
early  brief  one,  during  which  the  young  material  is 
produced,  then  the  later  and  prolonged  one,  in  which 
the  process  of  differentiation  goes  on,  and  that  which 
was  young,  through  a  prolonged  senescence,  becomes 
old.  I  believe  these  are  the  alternating  phases  of 
life,  and  that  as  we  define  senescence  as  an  increase 
and  differentiation  of  the  protoplasm,  so  we  must 
define  rejuvenation  as  an  increase  of  the  nuclear  ma- 
terial. The  alternation  of  phases  is  due  to  the  alter- 
nation in  the  proportions  of  nucleus  and  protoplasm. 
In  the  next  lecture  I  shall  be  able  to  convince  you, 
I  hope,  that  this  conception  of  the  relation  of  the 
power  of  growth  to  the  proportion  of  nucleus  and 
protoplasm  enables  us  to  understand  various  problems 


1 68  AGE,  GROWTH,  AND  DEATH 

of  development,  certain  possibilities  of  regeneration 
and  reconstruction  of  lost  parts,  and  that  it  also  leads 
us  naturally  forward  to  the  consideration  of  the  pro- 
blem of  death  as  it  is  now  viewed  by  biologists,  so 
that  our  next  lecture  will  be  upon  the  subject  of  re- 
generation and  death,  the  natural  topics  to  follow 
after  to-nieht's  discussion. 


V 

REGENERATION    AND    DEATH 

T  A  DIES  AND  GENTLEMEN:  In  the  last 
lecture  I  treated  the  conception  I  had  formed 
of  the  processes  of  regeneration  and  told  you  that  I 
looked  upon  the  change  which  occurred  first  in  the 
developing  germ  as  one  of  rejuvenation.  The  process 
has  for  its  technical  name  the  segmentation  of  the 
ovum.  The  appearance  of  the  segmentation  process 
was  illustrated  to  you  by  the  pictures  thrown  upon 
the  screen.  Cytomorphosis  is  a  term  which  we 
have  frequently  used  in  the  course  of  these  lectures, 
and  I  have  led  you,  I  hope,  to  the  appreciation  of  the 
idea  that  in  cytomorphosis  we  have  at  least  a  part  of 
the  explanation  of  old  age.  We  have  learned  that 
the  young  cells,  which  are  produced  by  the  segmenta- 
tion of  the  ovum,  are  in  large  part  changed  into  old 
cells,  and  also  that  old  cells  cannot  go  back  in  their 
development    and    again    become    young  ^ ;    so   that 

^  Pathologists  are  familiar  with  a  phenomenon  which  at  first  thought  might 
be  held  to  invalidate  this  assertion.  I  refer  to  the  growth  power  of  connective 
tissue  cells  under  certain  abnormal  conditions.  I  think  this  must  be  interpreted 
as  a  case  of  cellular  regeneration  effected  by  undifferentiated  protoplasm,  left 
over  in  each  cell  after  a  part  of  the  protoplasm  has  been  changed  into  fibrils, 
matrix,  etc.  In  brief,  the  process  involved  is  similar  to  that  in  the  regeneration 
of  striated  muscles,  described  later  in  this  lecture. 

169 


lyo  AGE,  GROWTH,  AND  DEATH 

one  might  easily  be  led  to  the  suspicion  that  there 
could  be  no  possible  new  young,  a  conclusion  ob- 
viously absurd,  for  there  Is  a  constant  renewal  of  the 
generations.  Some  device,  therefore,  must  exist  by 
which  that  which  is  young  is  perpetuated,  for  that 
which  is  old  cannot  again  become  young,  and  of  that 
device  I  should  like  to  say  something  this  evening. 

Formerly  the  notion  was  prevalent  that  under  suit- 
able conditions  old  cells  could  resume  the  young 
state  and  undergo  redifferentiation.  Hans  Dreisch,  E. 
Korschelt,^  and  a  few  other  contemporary  German 
and  American  writers  still  regard  the  occurrence  of 
retrogressive  development  i^'  Ent differ eiizirung'"^  as 
credible.  I  have  recently  been  over  the  few  cases  of 
alleged  evidence  in  favour  of  the  notion  in  question,  so 
far  as  they  are  known  to  me,  but  in  no  case  has  it 
been  proved  that  a  differentiated  cell  has  changed 
into  an  undifferentiated  one.  Provisionally,  at  least, 
we  can  maintain  that  there  is  no  exception  to  the  law 
that  an  old  cell  cannot  go  back  in  its  development. 
A  most  singular  theory  involving  the  assumption  of  the 
redifferentiation  of  cells  has  recently  been  enunciated 
by  a  German  author,  Kronthal,^  who  says  that  nerve 
cells  arise  each  by  the  fusion  of  several  white  blood 
corpuscles  {leucocytes)  into  a  single  mass.  In  answer 
to  him  it  may  be  said  :  firstly,  that  the  origin  of  nerve 

'  E.  Korschelt,  Regeneration  and  Transplantation,  Jena,  1907,  Gustav  Fischer. 
See  especially  pp.  76  and  99.  Compare  also  T.  H.  Morgan,  "  The  Physi- 
ology of  Regeneration,"  [ournal  of  Experimental  Zoology,  iii.,  p.  493  (1906). 

^  Kronthal,  Von  der  Nervenzelleun  der  Zelle  im  Allgemeinen,  8vo,  pp.  274, 
(1902,  G.  Fischer,  Jena).    Compare  also  Anatomischer  Anzeiger,  xxii.,  448. 


REGENERATION  AND  DEATH  171 

cells  from  the  embryonic  cells  of  the  nervous  system 
has  been  amply  proved  ;  secondly,  that  at  the  time  the 
nerve  cells  arise  no  outside  cells  enter  the  nervous 
system  ;  and,  thirdly,  that  the  nerve  cells  are  produced 
in  mammals  before  there  are  any  leucocytes  present 
in  the  embryo.  You  need  hardly  take  Kronthal's 
theory  seriously. 

As  a  preliminary  to  the  discussion  of  this  interest- 
ing phenomenon,  it  is  necessary  to  say  a  few  more 
words  in  regard  to  the  nuclei.  We  have  learned  that 
the  units  out  of  which  the  body  is  constructed,  the 
cells,  consist  each  of  a  little  mass  of  protoplasm  with 
a  central  body  called  the  nucleus  :  and  we  have  also 
learned  that  the  increase  of  the  protoplasm  and  the 
subsequent  differentiation  of  the  cell  is  to  be  looked 
upon  as  the  cause  of  old  age,  and  the  increase  of  the 
nucleus  as  the  cause  of  youth,  of  rejuvenation.  In 
addition  to  what  has  been  said  concerning  the  size  of 
the  nucleus,  some  further  explanation  is  necessary, 
and  that  can  best  be  given  with  the  aid  of  illustrations 
upon  the  screen.  The  first  of  the  pictures.  Fig.  59 
(seep.  164),  may  serve  to  recall  to  your  minds  what  I 
said  in  regard  to  the  process  of  the  segmentation  of 
the  ovum.  Here  is  an  ovum.  No.  i,  a  single  cell,  but 
relatively  of  enormous  size  ;  it  is  the  ovum  or  germ  of 
a  newt,  and  the  plate  illustrates  to  us  the  gradual  pro- 
cess of  division  of  the  original  single  cell  into  a  num- 
ber of  distinct  cells,  each  of  which  we  call  a  segment, 
and  the  formation  of  them  we  call  segmentation,  a 
name  which  we  keep  from  the  olden  time  when  the 


172  AGE,  GROWTH,  AND  DEATH 

process  was  first  observed  by  some  French  investiga- 
tors/ because  it  is  so  descriptive  of  tlie  appearance 
presented  to  the  eye  by  the  changes  which  are  going 
on.  Were  we  to  name  the  process  now  we  should 
certainly  call  it  a  process  of  cell  production. 

The  next  of  our  pictures  (Fig.  60)  shows  us  the 
eggs  of  a  common  animal,  the  Planorbis,  a  little 
fresh-water  snail,  the  coils  of  which  lie  flat  in  one 
plane — hence  its  name.^  No.  i  shows  the  original 
germ,  which  has  an  actual  diameter  of  0.132  ^mni.; 
No.  2  shows  it  about  to  divide  into  two.  No.  3  is  a 
side  view  and  No.  4  a  top  view  of  the  ovum  with  two 
segments;  No.  5  is  cleft  into  four  segments;  No.  6 
into  eight.  Nos.  7  and  8  illustrate  the  further  pro- 
gress of  the  cell  multiplication  ;  No.  9  represents  the 
under  side  of  the  same  ^gg,  of  which  the  top  is  figured 
as  No.  8.  The  number  of  cells  (segments)  is  thus 
constantly  increasing,  and  already  it  is  evident  that 
they  have  become  somewhat  unlike  in  character. 
The  pictures  were  made  from  the  living  ^'g'g,  and 
therefore  do  not  give  satisfactory  views  of  the  nuclei, 
but  nevertheless  there  is  during  segmentation  a 
change  going  on  in  them,  which,  however,  I  can  bet- 
ter demonstrate  to  you  by  means  of  Fig.  58.  Taken 
from    sections    through  the   early  developing  germ 

'  Especially  Prevost  and  Dumas,  "  Developpement  des  ceufs  des  batraciens," 
Annales  des  sciences  naturelles,  1842,  Tome  II.,  pp.  100  and  129,  and  earlier 
papers. 

'^  The  figures  are  copied  from  Carl  Rabl's  classic  memoir,  a  fine  monument 
of  capable  and  thorough  research  ;  see  "  Ueber  die  Entwickelung  der  Teller- 
schnecke,"  Morpholopsches  Jahrbuch,  v.,  561-655,  Taf.  XXXII.-XXXVIII, 


REGENERATION  AND  DEATH 


173 


of  a  mammal  named  Tarsius  spectabile.  It  is  a  crea- 
ture nearly  related  to  the  lemurs,  having  a  special 
interest  to  naturalists,  owing  to  the  fact  that  in   its 


Fig.  60.  The  Segmentation  of  the  Ovum  of  Planorbis,  to  show  the 
earliest  phases  of  development  of  the  egg  of  a  pond  snail ;  magnified  about  320 
diameters. — After  Carl  Rabl. 

early  development  it  offers  features  of  resemblance 
to  man  which  are  very  striking  and  instructive.  The 
plate  is  from  a  series  of  drawings  made  under  the 


174  AGE,  GROWTH,  AND  DEATH 

direction  of  Professor  Hubrecht,  the  principal  student 
of  the  development  of  this  type  of  animal.  Here, 
No.  I,  we  can  see  an  early  stage  in  which  the  germ 
consists  of  but  a  single  cell,  and  at  this  point  is  the 
nucleus.  Note  its  size  and  then  compare  it  with  the 
nuclei  in  No.  2,  in  which  several  of  these  cells,  as 
they  appear  in  a  section,  are  represented.  The  cells 
themselves  are  now  smaller  because  they  have  multi- 
plied by  the  division  of  the  original  germ,  but  the 
nuclei  in  them  are  likewise  smaller ;  and  in  the  older 
stage,  No.  3,  where  the  number  of  cells  has  begun 
still  further  to  increase,  we  see  that  there  is  another 
and  more  marked  reduction  in  the  size  of  the  nuclei. 
Contrast  the  single  nucleus  of  the  early  stage  with 
the  small  nuclei  of  the  later  one,  and  notice  how  very 
striking  is  the  change  in  the  size.  Thus,  during  the 
early  development  of  Tarszus,  we  find  that  there  is 
an  actual  rapid  reduction  in  the  size  of  the  nucleus. 
That  the  nuclei  become  smaller  during  the  segmenta- 
tion of  the  ovum  may  be  asserted  safely  to  be  a 
o-eneral  law.  I  have  examined  a  larg^e  number  of 
publications  in  which  the  segmentation  of  representa- 
tives of  the  principal  classes  of  the  animal  kingdom 
is  figured.  Without  exception  the  drawings  of  all 
the  authors  show  the  fact,  but  very  rarely  have  I 
found  even  an  allusion  in  the  text  to  the  progressive 
alteration  in  the  diameters  of  the  nuclei.  The  only 
author  known  to  me  who  has  explicitly  recognised 
the  invariable  occurrence  of  the  change,  and  who  has 
clearly  emphasised  its  importance,  is  Professor  Richard 


REGENERATION  AND   DEATH  175 

Hertwig  of  Munich.  As  we  have  learned  that  the 
proportion  of  the  nucleus  and  the  protoplasm  is  so 
important,  we  must  attribute  to  this  alteration  in  the 
dimensions  of  the  nucleus  during  segmentation  great 
significance. 

We  have  next  a  series  of  fiofures  which  have  inter- 
ested  me  very  much  and  which  I  only  recently  secured 
as  the  result  of  studies  I  have  been  making  in  my  own 
laboratory  at  the  Harvard  Medical  School.  These 
pictures  are  now  shown  publicly  for  the  first  time,  and 
record  a  fact  which,  so  far  as  I  know,  has  never  yet 
been  clearly  noted  and  recognised  as  important  by  any 
Investigator.  The  four  drawings  at  the  top,  Fig.  61, 
represent  four  single  nuclei  taken  from  different  parts 
of  a  rabbit  seven  and  one  half  days  after  the  com- 
mencement of  its  development.  The  second  set  of 
drawings,  5,  6,  7,  8,  show  nuclei  from  different  char- 
acteristic parts  of  a  rabbit  embryo  of  ten  days.  Note, 
please,  the  size  of  these  nuclei,  the  curious  network  of 
threads  in  their  interior,  and  the  existence,  generally 
more  or  less  in  a  central  position,  of  a  mass  of  material 
which  stands  out  conspicuously  and  represents  a  con- 
densation of  the  nuclear  stuff  at  that  particular  point. 
Such  a  central  body  is  highly  characteristic  of  these 
early  stages.  Next  we  come  in  the  series  of  draw- 
ings from  9  to  20,  stretching  across  the  screen  in  two 
lines,  to  a  rabbit  embryo  of  twelve  and  one  half  days. 
Instead  of  havine  nuclei  of  laro^e  size  we  have  now 
nuclei  which  are  obviously  small.  Instead  of  having 
nuclei  which  are  more  or  less  alike  in  appearance,  we 


Fig.  6i.  Nuclei  from  Rabbit  Embryos,   1-4,  age,  seven  and  one  half  days; 

5-8,  age,  ten  days.     9-20,  age,  twelve  and  one  half  days.     21-33,  age,  sixteen 

and  one  half  days. 

I,  ectoderm  ;  2,  mesoderm  ;  3,  entoderm  ;  4,  Hensen's  knot;  5,  ento- 
derm; 6,  mesenchyma;  7,  entoderm;  8,  medullary  groove;  g,  ectoderm; 
10,  large  motor  neurone;  11,  spinal  ganglion;  12,  mesenchyma;  13, 
cartilage;  14,  Wolffian  body;  15,  kidney;  16,  striated  muscle;  17,  heart 
muscle;  18,  esophageal  entoderm;  19,  tracheal  entoderm;  20,  liver;  21, 
ectoderm;  22,  motor  neurone;  23,  spinal  ganglion;  24,  dermis;  25, 
hypodermis;  26,  cartilage;  27,  28,  Wolffian  tubules;  29,  pelvis  of  kid- 
ney; 30,  heart  muscle;  31,  esophageal  entoderm ;  32,  tracheal  entoderm; 
33,  liver, 

176 


REGENERATION  AND   DEATH  177 

have  now  nuclei  of  great  diversity.  Every  one  of 
these  nuclei,  as  you  will  readily  see  if  you  run  your 
eye  along  from  one  end  of  the  lines  to  the  other, 
has  a  distinctive  character  of  its  own.  In  this  period, 
then,  of  two  and  one  half  days,  there  has  been  a 
revolution  in  the  character  of  the  nuclei  of  the  devel- 
oping embryo.  Where  before  the  nuclei  were  alike, 
now  they  have  become  unlike.  Two  of  these  I  should 
like  especially  to  call  your  attention  to,  because  they 
are  the  nuclei  of  the  nerve  cells — this  one.  No.  11, 
from  the  spinal  cord,  and  the  right-hand  one.  No.  10, 
from  the  cluster  of  nerve  cells  upon  the  root  of  a 
spinal  nerve.  Finally  we  have  the  series  of  drawings 
from  a  rabbit  of  sixteen  and  one  half  days  represented 
in  the  two  lower  rows,  21  to  33.  In  these,  if  you  will 
leave  aside  from  consideration  for  the  moment  22  and 
23,  which  are  obviously  of  a  different  size,  all  are 
now  smaller  than  they  were  at  twelve  and  one  half 
days.  Every  one  of  the  nuclei  here  represented  is 
characteristic.  We  have  here,  for  instance,  27,  28, 
nuclei  of  the  excretory  organ,  a  nucleus  of  the  con- 
nective tissue,  24  ;  we  have  nuclei  from  the  lining  of 
the  wind-pipe,  32;  and  the  lining  of  the  gullet,  31. 
Every  one  of  them  differs  from  every  one  of  the 
others  pictured.  But  if  we  had  drawings  of  a  number 
of  nuclei  from  the  same  part  of  the  body  and  same 
kind  of  tissue,  we  should  see  that  they  would  be 
essentially  similar.  We  learn  then  that  there  is  ac- 
quired a  great  diversity  in  the  structure  of  the  nuclei 
as  well  as  in  that  of  the  protoplasm,  of  which  we  have 


178  AGE,  GROWTH,  AND  DEATH 

seen  so  many  examples  in  the  previous  lectures. 
You  will  recall  that  as  regards  the  size  of  cells,  the 
nerve  cells  present  a  noteworthy  exception  in  that  they 
differ  according-  to  the  size  of  the  animal ;  and  their 
nuclei  differ  also,  for  as  the  cells  become  big  the  nu- 
clei grow  likewise.  Here  are  nerve-cell  nuclei,  loand 
1 1,  in  the  rabbit  of  twelve  and  one  half  days,  not  dif- 
fering in  their  dimensions  essentially  from  the  nuclei 
of  other  types,  but  in  the  two  lower  figures,  22  and 
23,  we  see  nuclei  of  corresponding  cells  of  the  rabbit 
at  sixteen  and  one  half  days.  These  cells  have  begun 
to  enlarge,  to  assume  the  greater  dimensions  of  the 
nerve  cells  which  are  characteristic  of  the  rabbit  when 
adult ;  and  accompanying  the  enlargement  of  the  cells 
there  has  been  an  expansion  of  the  nuclei  also.  But 
this  does  not  affect,  as  you  will  readily  see  by  the 
pictures  upon  the  screen,  the  nuclei  of  any  other  sort 
of  tissue,  the  nuclei  of  any  other  organ  of  the  body. 

The  differentiation  of  nuclei  has  been  little  studied. 
We  have  the  valuable  observations  of  Eycleshymer 
on  the  nuclei  of  muscles,  which  I  have  already  cited.  I 
know  of  no  other  exact  work  except  in  regard  to  the 
nuclei  of  nerve  cells,  the  genetic  changes  in  which  have 
been  recently  studied  with  care  by  Bombici,  Olmer, 
Hatai,  Marinesco,  Lache,  and  Remy  Collin. ^  The  paper 

'  Bombici,  "  Sui  caratteri  morfologici  della  cellula  nervosa  durante  le 
sviluppo.  Osservazioni  eseguite  suU'  embrione  di  polio,"  Archivio  Sci. 
Mediche,  xxiii.,  101-125  (1899). 

D.  Olmer,  "  Quelques  points  concernant  Thistogenese  de  la  cellule  nerveuse," 
C.  R.  Soc.  Biologic,  Paris,  1S99,  pp.  90S-911. 

Shinkishi  Hatai,  "  A  Note  on  the  Significance  of  the  Form  and  Contents  of 


REGENERATION  AND  DEATH  179 

by  the  last-mentioned  author  deserves  special  men- 
tion. The  investigation  of  nuclear  genesis  will  lead, 
I  believe,  to  results  of  great  general  biological  im- 
portance. 

We  must  therefore  add  to  our  conceptions  in  regard 
to  the  relations  of  the  nucleus  and  protoplasm,  as 
quantitatively  expressed,  this  further  notion — that 
there  is  during  the  early  period  of  development  an 
actual  reduction  in  the  size  of  the  nucleus.  When 
this  reduction  has  taken  place  it  is  of  course  evident 
to  any  one  at  all  acquainted  with  the  principles  of 
cytology  that  the  cells  are  in  a  very  different  state 
from  theirs  before.  They  are  no  longer  such  cells  as 
they  were  when  the  nucleus  was  large,  and  the  nuclei 
in  the  different  parts  of  the  body  alike  in  character. 
Here  the  relations  are  fundamentally  changed.  We 
do  not  find  that  these  nuclei  ever  get  back  from  the 
complex  variety  of  organisation,  which  they  present 
to  us  in  later  stages,  to  the  earlier  condition  when  they 
were  all  alike  ;  yet  only  with  cells  of  this  uniform 
sort  does  development  begin.  We  should,  therefore, 
if  we  reasoned  only  from  the  data  which  I  have  thus 
far   presented  to  you,  come  to   the  conclusion   that 

the  Nucleus  in  the  Spinal  Ganglion  Cells  of  the  Foetal  Cat,"  Journ.  Cotnp 
Neurol.,  xiv.,  26-48  (1904). 

G.  Marinesco,  "  Recherches  sur  le  noyau  de  la  cellule  nerveuse  a  I'etat 
normale  et  pathologique,"  yourn.  fur  PsycJiol.  und  Neurol.,  v.,  151-172 
1905)- 

Jon  G.  Lache,  "Sur  le  nucleole  de  la  cellule  nerveuse,"  ^T"^^'^"-  '^^  Neu- 
rologie,  1905,  501-51 1. 

R.  Collin,  "Recherches  cytologiques  sur  le  developpement  de  la  cellule 
nerveuse,"  Le  Ne'vraxe,  viii.,  181-309,  pis.  iv.-vi.  (1906). 


i8o  AGE,  GROWTH,  AND  DEATH 

reproduction  would  be  impossible  ;  that  the  cells  of 
the  body,  having  been  so  changed,  as  we  have  seen, 
are  no  longer  capable  of  returning  backwards  along 
the  path  they  have  journeyed  ;  they  can  only  remain 
where  they  are,  or  go  yet  farther  onward  in  the  career 
of  cytomorphosis.  Nature,  however,  has  met  this 
difficulty  by  a  way  which  we  have  only  recently  dis- 
covered. We  are  not  yet  sure  that  the  way  we  have 
discovered  is  the  only  way,  that  it  is  the  universal 
method  in  the  case  of  all  animals  for  accomplishing 
the  purpose.  The  discovery  of  this  method  of  pro- 
viding for  the  perpetuation  of  youthfulness  from  one 
generation  to  another  is  due  to  the  investigations  of 
Professor  Nussbaum,  of  Bonn.^  The  theory  which 
he  put  forward  has  been  verified  by  subsequent 
examinations  and  investigation,  and  confirmed,  I  am 
glad  to  say,  in  part  by  some  very  interesting  and 
careful  observations  which  have  been  made  here  in 
Boston  by  Dr.  F.  A.  Woods,^  at  that  time  a  member 
of  my  laboratory  staff.  Perhaps  the  very  best  con- 
firmation of  all  is  the  recent  extension  of  our  know- 
ledge in  regard  to  this  theory  which  comes  from  the 
investigations  ^  of  Dr.  B.  M.  Allen,  made  at  Madison, 
on  the  perpetuation  of  germ  cells  in  the  developing 

*  M.  Nussbaum,  "  Ueber  die  Veranderungen  der  Geschlechtsprodukte  bis  zur 
Eifurchung  ;  ein  Beitrag  zur  Lehre  der  Vererbung,"  Archiv.  fiir  Mikrosk 
Anat.,  xxiii.,  155  ;  cf.  alsoxli.,  119. 

'^  F.  A.  Woods,  "Origin  and  Migration  of  the  Germ-cells  in  Acanthias^^ 
American  Jonrn.  of  Anat.,  vol.  i,  p.  307. 

^  Bennet  M.  Allen,  Science,  vol.  xxi.,  p.  850  (1905);  Amer.  yourn.  of 
Anatomy,  vol.  v.,  pp.  79-94  ;  Anatomischer  Anzeiger ,  xxix.,  217,  and  xxx.,  391  ; 
and  on  the  frog,  see  Aiiatoinischer  Anzeiger,  xxxi.,  339-347  (1907). 


REGENERATION  AND  DEATH  i8i 

turtle  and  frog.^  It  is  really  essentially  a  very  simple 
thing.  Nature  seems  to  take  some  of  the  cells  which 
are  in  the  primitive  condition,  with  the  protoplasm 
still  undifferentiated  and  the  nucleus  of  the  embryonic 
or  simple  organisation,  and  hold  them  apart  from  the 
rest  of  the  body  ;  not  separating  them  so  that  they 
come  off  and  leave  the  body,  but  so  that  they  have  a 
different  history,  so  that  they  escape  the  change  which 
the  other  cells  of  the  body  must  pass  through.  These 
cells  of  a  simpler  character,  which  have  been  named 
germ  cells  or  sex  cells,  are  gathered  together,  kept 
asunder  for  a  while  from  all  the  other  cells  of  the 
body,  and  never  allowed  to  share  in  the  development 
of  the  other  cells  which  form  the  body  proper.  For 
instance.  Dr.  Woods  discovered  that  in  the  develop- 
ment of  the  dog-fish,  very  early,  before  any  organs 
exist,  the  germ  cells  are  formed  into  a  cluster  (Fig. 
62).  They  lie  by  themselves,  are  easily  recognised 
under  the  microscope,  and  they  have  obviously  the 
primitive  character  which  I  have  endeavoured  to  ex- 
plain to-  you,  and  which  they  long  retain.  Meanwhile, 
as  development  progresses,  all  the  remaining  cells — 
all  those  not  part  of  these  clusters — pursue  their 
proper  careers,  become  differentiated  ;  but  the  cells 

^  In  birds,  although  closely  related  to  reptiles,  the  relations  are  less  clear  than 
in  turtles.  Germ  cells  in  an  early  stage  (chick  of  two  days'  incubation  with 
26-30  primitive  segments)  occur  in  the  rudiment  of  the  wall  of  the  intestine 
(splanchnopleure),  as  they  do  secondarily  in  the  turtle,  and  from  there  migrate 
during  later  stages  as  in  the  turtle  into  the  sexual  glands.  Unfortunately  their 
earlier  history  has  not  been  traced.  See  W.  Rubaschkin,  Ueber  das  erste 
^tiftreten  und  Migration  der  Keimzellen  bei  Vogel-e?nbryonen,  Anat.  Hefte. 
Erste  Abth.,  xxxv.,  pp.  241-262,  Taf.  1-3  (1907). 


I»2 


AGE,  GROWTH,  AND  DEATH 


in  the  clusters  do  not  change  for  a  long  period. 
Later,  as  the  organs  become  differentiated,  we  can 
recognise   in  the  direct  descendants  of  these  cells, 


Ent 


Germ  Cells 


Fig.  62.  Section  across  the  Posterior  Part  of  an  Embryo  Dog-fish 
{Acanthias)  of  3.5  mm.,  to  show  the  compact  chister  of  germ  cells  on  one  side. 
The  germ  cells  in  later  stages  migrate  from  this  primitive  position,  moving 
singly  or  in  small  groups.  Ect,  ectoderm  ;  Md,  medullary  canal  or  primitive 
spinal  cord ;  Nch,  notochord  ;  Mes,  mesoderm ;  Ent,  entoderm  ;  X,  cellular 
strand  connecting  the  germ-cell  cluster  with  the  yolk,  (From  the  Harvard 
Embryological  Collection,  Series  463,  Section  147.  Already  figured  by  Dr.  F. 
A.  Woods,  but  with  a  lower  magnification.) 


which  have  been  traced  from  stage  to  stage  so  that 
their  history  is  known  with  certainty,  those  cells  which 
in  the  adult  we  call  the  germ  cells,  and  which  are  to 


REGENERATION  AND  DEATH  183 

serve  for  the  reproduction  of  the  species.  These  cells 
are  set  apart  at  all  periods.  They  represent  germinal 
matter  which  is  withheld  from  the  metamorphosis 
which  the  rest  of  the  body  undergoes.  They  have 
a  continuous  history.  Hence  we  bestow  upon  this 
method,  under  the  conception  that  it  is  applied  to 
secure  propagation  of  the  species,  the  term — theory 
of  germinal  continuity.  It  is  the  theory  of  hereditary 
transmission,  which  I  think  is  now  universally  held 
by  all  competent  biologists.  Our  study  of  nuclei  and 
of  their  relations  to  protoplasm  serves  to  clear  up  in 
our  minds,  it  seems  to  me,  to  some  degree  at  least, 
the  necessity  which  really  exists  for  this  device  of 
germinal  continuity,  of  the  setting  apart  of  certain 
cells  of  the  rejuvenating  sort,  of  the  young  sort,  of 
the  embryonic  type  (the  term  you  apply  to  them 
matters  little),  which  cells  are  those  used  to  produce 
the  new  offspring  of  the  next  generation.  All  this, 
of  course,  fits  perfectly  with  the  doctrine  which  I 
have  been  telling  you  of  again  and  again  in  this  course 
of  lectures,  that  the  progress  of  differentiation  is  al- 
ways in  one  direction  and  ends  in  the  production  of 
structure  which,  if  it  is  pursued  to  its  legitimate  ter- 
minus, results  in  the  degeneration  and  death  of  the 
cell.  Obviously  cytomorphosis  cannot  produce  the 
sort  of  a  cell  which  is  necessary  for  reproduction. 

I  wish  there  were  time  to  enter  more  fully  into  the 
question  of  the  size  of  nuclei,  for  there  is  much  which 
might  be  said  concerning  it.  This  much  more,  how- 
ever, ought  to  be  said  to  you — that  the  problem  of 


1 84  AGE,  GROWTH,  AND  DEATH 

the  size  of  nuclei  is  by  no  means  a  simple  one.  It 
has  been  found,  for  instance,  in  the  experiments  made 
upon  some  of  the  simple  algae,  the  so-called  Spirogyra, 
which  every  elementary  student  of  botany  probably 
has  looked  at  in  the  laboratory,  that  by  certain  arti- 
ficial conditions,  as  made  in  the  experiments  of  Pro- 
fessor Gerassimow,^  the  size  of  the  nucleus  can  be 
changed  in  the  cells,  and  when  the  size  of  the  nucleus 
is  changed,  the  size  of  the  cell  alters  also.  Professor 
Richard  Hertwig  has  made  some  very  interesting 
experiments,^  proving  that  in  the  case  of  certain  pro- 
tozoa, the  size  of  the  nucleus  varies  with  the  tempera- 
ture ;  he  says  of  Dilepta,  the  form  experimented  on, 
"  Kiihle  Temperatur  veranlasst  grosse,  warme  Tem- 
peratur  kleine  Kerne"  (p.  lo).  We  considered  a  few 
moments  ago  the  reduction  in  the  size  of  nuclei  dur- 
ing the  early  stages  of  the  embryonic  development. 
Later,  however,  there  is  again  an  increase  of  size  in 
the  nuclei,  occurring  during  the  later  embryonic 
development  and  during  youth.  Recently  K.  A. 
Heibere^  has  pfiven  some  data,  from  which  I   have 

'  J.  J.  Gerassimow,  "  Ueber  den  Einfluss  des  Kerns  auf  das  Wachsthum  der 
Zelle,"  Bulletin  Soc.  Impe'r.  Naturalistes,  Moscozi,  igoo,  pp.  1S5-220. 

"  Die  Abhangigkeit  der  Grosse  der  Zelle  von  der  Menge  ihrer  Kernmasse," 
Zettschrift  f.  allgem.  Physiologic,  i.,  220-258. 

"  tjber  die  Grosse  des  Zellkemes,"  Beihefte  z.  Botan.  Centralblatt,  xviii., 
45-118. 

"  Zur  Physiologie  der  Zelle,"  Bulletin  Soc.  Impe'r.  Naturalistes,  Moscou, 
1904,  pp.  1-134. 

^  Richard  Hertwig,  "  Ueber  das  Wechselverhaltniss  von  Kern  und  Proto- 
plasm a  "  (see  pages  10  ff.),  Sitzungsbcr.  Gcsell.  Alorphol.,  Munchen,  1902-3. 

^  K.  A.  Heiberg,  "  Ueber  eine  erhohte  Grosse  der  Zelle  und  deren  Theilebei 
dem  ausgewachsengn  Organismus,  verglichen  mit  dem  nicht  ausgev/acbsenen," 


REGENERATION  AND  DEATH  185 

calculated  the  sizes  of  nuclei.     His  observations  were 
on  the  liver  and  pancreas  of  white  mice.     The  figures 


New  born 

Half  grown 

Full  grown 

Liver 

5-9/^ 

6.2  yK 

S.2  n 

Pancreas 

5.06  IJ. 

S-15  1^ 

in  the  table  give  the  average  diameters,  based  in  each 
case  on  the  measurement  of  fifty  nuclei.  Professor 
Hertwig,  in  the  article  just  referred  to,  has  demon- 
strated that  for  each  kind  of  cell  there  is  a  characteristic 
proportion  between  the  nucleus  and  the  protoplasm, 
so  that  large  cells  have  large  nuclei,  and  small  cells 
have  small  nuclei.  This  conception  is  certainly  most 
valuable,  and  if  we  make  the  necessary  allowance  for 
the  change  in  proportion  during  cytomorphosis,  it 
seems  to  be  fully  justified  by  the  facts.  And  again, 
we  know  that  the  nucleus  provides  certain  chemical 
supplies  for  the  life  and  functioning  of  the  cells.  This 
is  very  strikingly  the  case,  for  instance,  in  regard  to 
the  cells  which  secrete.  These,  when  they  give  off 
the  material  which  they  have  accumulated  in  their  pro- 
toplasm as  a  preparation  for  the  act  of  secretion,  are 
found  not  only  to  reduce  the  bulk  of  their  protoplas- 
mic bodies,  but  the  bulk  of  the  nuclei  as  well.  And 
we  know  again  that  the  size  of  nuclei  may  be  changed 
by  somatic  conditions,  by  food  supply,  so  that  in  every 
generalisation  reached  by  the  study  of  the  size  of 

Anatomische  Atizeiger,  xxxi.,  306-311  (1907).  It  is  singular  that  the  author  has 
not  reduced  his  measurements  so  as  to  give  the  absolute  dimensions  of  the 
nuclei.  By  supplying  this  omission  I  have  obtained  the  values  given  in  th§ 
main  text. 


1 86  AGE,  GROWTH,  AND  DEATH 

nuclei,  we  must  be  very  circumspect,  and  not  fancy 
too  easily  that  we  have  reached  a  safe  conclusion  un- 
less we  have  taken  into  consideration  all  the  possible 
factors  by  which  the  size  may  have  been  varied. 

In  what  I  have  said  to  you  hitherto  in  regard  to 
the  power  of  growth,  I  have  directed  your  attention 
chiefly  to  the  power  of  growth  as  it  exists  in  a  cell  in 
consequence  of  that  cell's  condition.  When  the  cell 
is  in  the  young  state,  it  can  grow  rapidly  ;  it  can  mul- 
tiply freely ;  when  it  is  in  the  old  state  it  loses  those 
capacities,  and  its  growth  and  multiplication  are  cor- 
respondingly impeded,  and  if  the  organisation  is  car- 
ried to  an  extreme,  the  growth  and  the  multiplication 
of  the  cell  cease  altogether. 

We  find,  however,  that  it  is  not  merely  a  question  of 
the  capacity  of  the  cells,  but  also  of  the  exercise  of  that 
capacity,  which  we  must  deal  with.  Here  enters  a  factor 
of  which  we  learn  from  the  study  of  regeneration.  The 
phenomena  of  regeneration  are  important  and  very  in- 
structive. We  shall  come  to  them  presently.  It  will 
make  our  study  of  regeneration  clearer,  more  signifi- 
cant, I  think,  if  we  pause  for  a  moment  to  consider 
certain  fluctuations  in  the  natural  development  of  the 
organism.  We  see,  for  instance,  in  the  brain  that  early 
the  cells  beein  to  assume  the  character  of  nerve  cells  and 
that  thereafter  their  multiplication  ceases.  But,  cur- 
iously, there  will  be  a  spot  in  the  spinal  cord,  for  ex- 
ample, where  the  change  of  the  cells  into  nerve  cells 
has  not  taken  place,  and  from  that  growth  will  go  on. 
Cells  will  migrate  from  that  spot  and  reach  their  ulti- 


REGENERATION  AND  DEATH  187 

mate  destination.  When  the  child  is  born  it  is  incapable 
of  movement.  There  is  scarcely  more  than  the  power 
of  twitching  about  in  a  disorderly  fashion.  Its  muscles 
can  contract,  to  be  sure,  but  any  sort  of  motion  that 
implies  a  harmonious  working  together  of  various 
muscles,    the   baby   at   birth    is   quite   incapable   of. 


moh. 


Fig.  63.  Section  of  the  Cerebellum  of  a  Child  of  Thirteen  Days. 
Only  the  nuclei,  which  are  represented  as  black  dots,  are  drawn,  o.  /. ,  outer 
layer,  which  disappears  during  childhood;  tnol,  molecular  layer;  gr,  granular 
layer.     X    120     diams. 

This  phenomenon  is  doubtless  due  to  the  fact  that 
the  cerebellum,  the  small  brain,  is  as  yet  imperfectly 
developed.  If  we  examine  the  brain  of  the  child  at 
birth,  we  find  at  the  edge  of  the  cerebellum  a  line  along 
which  the  production  of  new  cells  is  going  on.  These 
new  cells  migrate  over  the  surface  of  the  cerebellum 


i88  AGE,  GROWTH,  AND  DEATH 

without  changing  at  all  into  nerve  cells.  They  form 
a  distinct  layer,  Fig.  63,  which  is  well  known  to  every 
investigator  of  brain  structure.  Soon  after  birth 
these  cells  accomplish  a  second  migration,  but  in  a 
different  direction.  Instead  of  moving  in  a  constant 
current  over  the  surface  of  the  brain,  each  one  takes  a 
vertical  pathway  from  the  surface  down  towards  the 
interior  of  the  cerebellum  ;  and  arrived  there,  it  changes 
and  becomes  a  nerve  cell,  or  at  least  a  part  of  them 
do  ;  and  with  that  the  machinery  of  the  cerebellum  is 
complete.  Thus,  structurally,  the  cerebellum  at  birth 
is  an  uncompleted  organ.  Now,  the  cerebellum  is 
that  portion  of  the  brain  which  regulates  the  combina- 
tion of  muscular  movements,  which  secures  what  the 
physiologists  term  co-ordination  of  movements,  and  it 
is  not  until  the  cerebellum  has  been  perfected  that  it 
can  perform  this  function.  Were  there  not  some  pro- 
vision of  this  special  sort  for  allowing  cells  to  be 
produced  and  added  to  the  brain,  the  full  complexity 
of  the  brain  could  not  be  attained,  because  after  the 
cells  have  begun  to  change  into  nerve  cells  they  lose 
their  power  of  multiplication,  and  this  is  a  device  very 
exquisite  in  its  working  to  supply  to  the  brain  the 
number  of  cells  needed  to  give  it  its  full  measure  of 
complexity. 

Another  instance  of  the  reservation  of  cells  of  a 
simple  type  is  afforded  us  by  the  skin,  about  which  I 
shall  have  something  more  to  say  in  a  few  moments 
when  we  speak  of  the  process  of  regeneration.  It  is 
not  only  in  the  period  of  childhood,  and  not  only  in 


REGENERATION  AND  DEATH  189 

the  cerebellum,  that  we  find  cells  exist  such  as  I  have 
just  described  to  you,  but  it  is  in  other  parts  of  the 
body  also  and  at  other  periods  of  life  that  we  find  the 
like  phenomena  ;  and  in  part  I  have  already  referred  to 
these.  You  remember  I  told  you  in  a  previous  lecture 
that  there  is  always  in  the  body,  even  at  the  extreme 
of  life,  a  store  of  cells  of  the  young  type,  which  is 
garnered  in  the  marrow  of  the  bones.  The  cells  in 
question  can  multiply,  and  their  descendants  in  part 
undergo  a  change  in  consequence  of  which  they  are 
converted  into  blood  corpuscles.  The  undifferentiated 
or  young  cells  are  preserved  in  the  marrow  precisely 
for  the  purpose  of  making  up  the  necessary  number  of 
blood  corpuscles  to  replace  those  which  are  lost  either 
by  accident  or  in  consequence  of  normal  physiological 
processes. 

We  can  speak  in  more  general  terms.  In  the  very 
early  stages  of  the  embryo  the  growth  is  diffuse,  or — 
as  it  is  sometimes  termed  technically — interstitial.  Of 
course  growth  depends  upon  cell  multiplication,  and 
when  we  say  growth  is  diffuse,  we  mean  that  cell  di- 
vision takes  place  throughout  the  organ  or  tissue.  For 
example,  in  the  three  germ  layers,  in  a  stage  preced- 
ing the  differentiation  of  organs,  we  find  the  mitotic 
figures  (which  prove  active  cell  division)  to  be  scat- 
tered about.  They  may  occur  in  any  part  of  each  layer. 
As  development  progresses  the  growth  becomes  in 
many  parts  focal,  that  is  to  say,  there  are  established 
centres  of  growth,  at  each  of  which  the  multiplication 
of  cells  proceeds,  while  in  the  immediately  surround- 


Fig.  64  A.  Section  of  a  Lens  of  the 
Eye  of  a  Chick  of  68  Hours'  Incuba- 
tion. A,  outer  or  anterior  wall;  jS,  inner 
or  posterior  wall.  The  dark  irregular 
spots  show  the  distribution  of  the  mitotic 
figures.     C,  central  cavity.     350  diameters. 


Fig.  64  B.  Section  of  a  Lens  of  the  Eye  of  a 
Chick  of  96  Hours'  Incubation.  A,  outer  wall; 
B,  inner  wall;  C,  central  cavity.  The  dark  irregular 
spots  show  the  distribution  of  the  mitotic  figures. 
350  diameters. 


190 


REGENERATION  AND  DEATH  191 

ing  parts  it  ceases.  In  all  the  cases  known  to  me  the 
cells  in  the  foci  of  growth  are  small  and  embryonic  in 
character,  while  the  surrounding  cells,  which  do  not 
multiply,  are  larger  and  more  or  less  differentiated. 
Fig.  64  illustrates  the  matter.  The  drawing  on  the 
left,  A,  represents  the  beginning  {Anlage)  of  the  lens 
of  a  chicken  embryo,  as  seen  in  section.  The  mitotic 
figures,  produced  by  the  dividing  cells,  are  scattered 
and  may  occur  anywhere.  The  drawing  on  the  right, 
B,  represents  a  section  of  a  differentiated  but  still  grow- 
ing lens.  The  inner  layer,  B,  has  completely  changed 
owing  to  the  differentiation  of  its  cells,  which  have 
been  transformed  into  lens  fibres  and  no  longer  mul- 
tiply. The  outer  layer.  A,  on  the  contrary  is  still  un- 
differentiated and  that  its  cells  are  still  capable  of 
muliplication  is  evidenced  by  the  mitotic  figures  scat- 
tered throuo-h  it.  The  mitotic  figures,  owino-  to  their 
deep  staining,  are  conspicuous.  The  main  volume  of 
the  structure  is  formed  by  lens  fibres,  each  of  which  is 
a  differentiated  cell  and  has  never  been  found  in  pro- 
cess of  cell  division.  Only  at  its  edge  can  the  inner 
layer  of  the  lens  acquire  new  elements;  the  cells  there 
produced  are  added  to  it  and  give  rise  to  additional 
lens  fibres.  In  A,  we  observe  the  lens  growing  inter- 
stitially;  in  B,  by  apposition.  Appositional  growth 
plays  many  important  roles  in  the  ontogeny  of  verte- 
brates.i     It  occurs  in  the  retina,  in  the  enamel  organ 

'  Schaperund  Cohen,  "Beitrage  zur  Analyse  desthierischen  Wachsthume,"  II. 
Theil,  Arch,  fiir  EntwickeLu7igs-?necha)iik,  xix.,  348-445(1905).  This  article 
gives  a  clear  exposition  of  the  distinction  between  diffuse,  or  interstitial,  and  focal. 


192  AGE,  GROWTH,  AND  DEATH 

of  teeth,  in  the  spinal  cord,  and  in  many  other  cases. 
In  all  of  these  instances  the  focus  of  cell  production 
might  be  described  aptly  as  a  growth-zone.  In  many 
other  instances  the  growth  centres  are  very  small.  For 
example,  at  the  root  of  every  hair  there  is  such  a 
centre.  The  hair  grows  exclusively  at  its  base ;  the 
steady  addition  of  new  cells  forces  the  older  ones  up, 
lengthening  the  hair.  Every  little  gland  in  the  stomach 
and  intestines  has  its  own  growth  centre.  Each  of  the 
glands  in  question  is  a  minute  tube  from  one  to  two 
millimetres  in  length,  with  its  orifice  (Fig  65),  at  the 
inner  surface  of  the  digestive  tract;  the  opposite  end, 
or  base,  ends  blindly.  We  have  now  before  us  a  picture 
of  a  gland  from  the  large  intestine  of  a  cat.  It  is  seen 
in  vertical  section.  The  irregularly  shaped  dark  spots, 
mi,  represent  dividing  nuclei,  and  they  are  all  located 
near  the  bottom  of  the  pfland.^  As  the  new  cells  are 
produced  the  older  ones  are  shoved  up  towards  the 
orifice  and  undergo  differentiation.     After  getting  to 

or  appositional  growth.  This  investigation  was  one  which  I  suggested  to  Dr. 
Schaper,  while  he  was  a  member  of  my  staff  at  the  Harvard  Medical  School,  and  I 
pointed  out  to  him  the  difference  involved  between  the  two  types  of  growth  and 
the  bearing  of  it  on  the  general  notions  which  I  had  already  formed  and  in  part 
published  at  that  time.  I  also  called  his  attention  to  a  number  of  the  specific 
illustrations  which  he  and  Cohen  studied.  I  regret  that  Dr.  Schaper  has  failed  in 
this  paper  to  mention  the  actual  source  of  the  general  conceptions  which  he  has 
put  forward  as  original  with  himself.  The  research  by  Schaper  and  Cohen  is  an 
excellent  piece  of  work  and  contains  much  that  is  new. 

'  The  manner  in  which  intestinal  and  gastric  glands  grow  was  discovered  by 
Bizzozero,  "SuUeghiandoli  tubulari  del  tubo  gastro-enterico,  etc.,  Nola  prima," 
Aiti  Accad.  Sci.  Torino,  xxiv.,  110-137,  Tav.  III.  (188S).  lie  has  also  written 
several  subsequent  articles, — see  especially  ^rr/zm  y>V;- w//'ri7j/('.  Anat.,y\\\., 
82-152,  Taf.VII.-IX.  His  observations  have  been  abundantly  confirmed  by  later 
investigators. 


Fig.  65.     Section  of  a  Gland  of  the 

Large  Intestine  of  an  Adult  Cat.  or, 

orifice  of   the  gland,    wz,    dividing   nuclei 

(mitotic  figures).     130  diameters.. 

193 


194  AGE,  GROWTH,  AND  DEATH 

the  top,  the  cells  are  cast  off.  I  have  already  spoken 
of  the  enormous  loss  of  cells  from  the  lining  of  the 
digestive  canal  which  occurs  throughout  life. 

I  could  multiply  these  instances  almost  indefinitely, 
but  perhaps  it  will  be  better  to  call  your  attention  to 
an  illustration  of  quite  a  different  sort.  We  know 
that  in  order  to  have  a  very  complex  organisation, 
the  number  of  cells  in  the  body  must  be  very  large 
indeed.  Obviously  a  small  insect,  a  mosquito  or  a 
little  beetle,  whatever  it  may  be,  is  not  big  enough  to 
have  a  great  many  cells ;  and,  unless  it  has  a  great 
many,  it  cannot  attain  the  differentiation  of  compli- 
cated organs  such  as  we  possess.  Now,  the  lower 
animals  are  born,  so  to  speak,  early,  and  as  soon  as 
they  hatch  out,  they  have  to  support  themselves.  We 
see  that,  for  instance,  in  caterpillars.  They  are  born 
very  little  creatures,  but  each  tiny  caterpillar  must 
take  care  of  itself,  obtain  its  own  food,  move  about  to 
that  food,  must,  when  the  food  is  swallowed,  digest  it, 
and  must  carry  on  the  correlated  functions  of  secre- 
tion and  excretion  ;  it  must  breathe.  In  order  to  do 
all  this  the  larva,  or  young  caterpillar,  to  follow  our 
special  instance,  must  have  some  differentiation  al- 
ready established ;  but,  as  we  have  learned,  differen- 
tiation impedes  growth.  In  other  words,  in  such  a 
larva  the  multiplication  of  cells  is  held  back  by  the 
very  demands  of  the  condition  of  its  existence.  If  it 
is  to  have  organs  which  are  to  function,  it  must  have 
differentiated  parts,  and,  if  it  is  differentiated,  its 
growth  power  must  be  sacrificed. 


REGENERATION  AND  DEATH  195 

How  has  nature  proceeded  in  order  to  produce  a 
higher  type  of  animal,  one  in  which  the  number  of  cells 
is  much  greater?  Very  ingeniously.  She  provides 
the  developing  organism  with  a  food  supply  which 
it  carries  itself.  If,  for  instance,  you  recall  the  &gg  of 
the  salamander,  which  I  showed  you  upon  the  screen, 
you  will  remember  that  that  is  a  structure  of  consider- 
able size,  and  its  size  is  due  to  the  accumulation  of 
food  material,  material  which  we  designate  by  the 
term  yolk  granules,  which  lie  in  the  living  protoplasm 
of  that  germ.  This  supply  of  food  is  so  great  that  it 
will  last  the  organism  a  considerable  period.  While 
it  is  growing  it  has  nothing  to  do  but  to  digest  that 
food  supply  which  it  already  possesses.  It  does  not 
have  to  exert  itself  to  obtain  it,  and  no  further  diges- 
tive process  is  necessary  than  that  inherent  in  all  living 
protoplasm.  So  the  young  salamanders  develop  under 
most  advantageous  conditions,  and  can  actually  pro- 
duce a  much  greater  number  of  cells  because  it  is 
possible,  with  this  internal  food  supply,  for  the  growth 
to  go  on  only  with  the  cells  of  the  embryonic  or 
youthful  type  for  a  considerable  period,  and  then, 
when  their  number  has  considerably  increased,  steps 
in  the  process  of  differentiation. 

In  the  higher  animals  the  accumulation  of  food  for 
the  nourishment  of  the  germ  is  carried  yet  further. 
As  you  know,  the  ^'gg  of  the  bird  is  much  bigger  than 
that  of  the  salamander.  Again,  in  the  highest  ani- 
mals, in  the  placental  mammals,  there  are  other  special 
contrivances  which  nature  has  introduced  to  secure 


196  AGE,  GROWTH,  AND  DEATH 

ample  and  adequate  nourishment  of  the  developing 
germ.  By  means  of  the  placenta  the  uterine  period 
has  been  lengthened,  and  the  embryo  is  nourished  at 
the  expense  of  the  mother  with  little  physiological 
exertion  on  its  own  part.  Moreover,  in  all  mammals 
lactation  and  maternal  care  serve  to  further  prolong 
the  developmental  period.  By  these  means  the  pro- 
tective processes  have  been  wonderfully  perfected  and 
the  result  is  that  in  mammals  there  is  a  long  period 
during  which  the  production  of  cells  goes  on  ;  the 
cells  at  first  all  remain  relatively  simple,  and  by  the 
time  they  begin  to  change  the  number  of  cells  is  so 
great  that  the  possibilities  of  an  almost  infinite  variety 
of  peculiarities  in  them  are  given.  There  are  cells 
enough  to  allow  this  variety  to  be  worked  out.  This 
type  of  development  we  call  the  embryonic.  We 
know,  therefore,  that  nature  has  recognised  a  restric- 
tion which  she  herself  has  put  upon  development,  the 
restriction  which  obliges  development,  if  it  is  to  be 
ample,  to  prolong  the  accumulation  of  the  undifferen- 
tiated cells.  In  response  to  this  condition,  she  has 
instituted  for  higher  types  of  animals  that  development 
which  we  call  embryonic,  leaving  for  the  lower  types 
that  development  which  we  call  larval.^  Thus  we 
meet  in  the  growth  and  formation  of  the  higher  ani- 
mals, and  in  the  history  of  the  comparative  develop- 


'  The  comparison  between  the  larval  and  embryonic  types  of  development 
was  first  made  by  me  in  1895,  "  Ueber  die  Vererbung  und  Verjiingung,''  Bio- 
logisches  Ceniralblatt.,  xv.,  571-5S7  ;  translation  in  American  Naturalist,  xxx., 
1-9,  89-101. 


REGENERATION  AND  DEATH  197 

ment  of  the  animal  kingdom,   fresh   illustrations  of 
the  great  importance  of  the  young  type  of  cells. 

We  can  learn  the  same  thing  from  the  study  of 
regeneration.  The  regenerative  process  depends  to 
a  large  extent  upon  partial  differentiation,  or  even 
upon  its  total  absence.  Regeneration  is  a  most  in- 
teresting and  wonderful  process.  I  took  pains  only 
this  afternoon  to  look  at  that  famous  classic  by 
Trembley  ^  on  hydroids,  or  polyps  as  he  called  them. 
T/ie  Fresh-  Water  Polyps,  a  book  published  in  1 744, 
was  well  printed,  and  on  such  good  paper  that  it 
looks  to-day  almost  like  a  new  book.  He  per- 
formed the  curious  experiment  of  cutting  one  of 
these  minute  fresh-water  polyps — they  are  perhaps  an 
eighth  of  an  inch  long — in  two,  and  made  the  start- 
ling discovery  that  each  half  of  the  polyp  would  make 
up  what  the  other  half  had  deprived  it  of ;  each  half, 
in  other  words,  would  become  a  new  polyp.  That 
which  was  lost  was  regenerated.  After  him  came  a 
series  of  yet  more  remarkable  experiments  by  the 
famous  Italian  naturalist,  Spallanzani,  one  of  the 
masters  of  experimental  research,  and  he  discovered 
that  regeneration  was  a  property  which  was  not 
peculiar  by  any  means  to  polyps,  but   existed  in  the 

^  Me'moire  pour  servir  a  V  histoire  d'  tm  genre  de  polypes  d'  eau  douce  a 
bras  en  forme  des  carnes,  par  A.  Trembley,  de  la  Societe  Roiale,  a  Leide, 
MDCCXLIV.,  4to,  pp.  xvi.,  324  ;  13  plates.  A  German  translation  by 
J.  A.  E.  Goeze  was  published  at  Quedlinburg  in  1775. 

Abraham  Trembley  was  born  at  Geneva,  Switzerland,  in  1700  and  died  there 
in  17S4.  His  famous  experiments  were  made  in  Holland  while  he  was  engaged 
as  a  tutor  in  the  family  of  Count  Bentinck. 


198  AGE,  GROWTH,  AND  DEATH 

earthworm,  and  even  among  vertebrates  ;  for  he  it 
was  that  proved  that  if  the  head  of  an  earthworm  be 
cut  off,  the  worm  will  form  a  new  head,  with  a  new 
brain  and  a  new  mouth.^  He  first  discovered  that 
if  you  cut  off  the  tail  or  the  leg  of  a  salamander,  a 
new  tail,  or  a  new  leg,  as  the  case  may  be,  would 
o-row  out.      He  also  made  similar  experiments  on  the 


Fig.  66.  Vignette  from  Trembley's  Classic  Memoir,  representing  Trembley 
making  his  experiments  on  regeneration  in  fresh-water  polyps. 

regeneration  of  the  tail  in  tadpoles.  He  it  was, 
moreover,  who  discovered  that  this  power  of  replacing 
the  lost  part  is  greater  in  the  young — greater  in  the 
earlier  stage  than  in  the  later.     These  examples  may 

*  Lazaro  Spallanzani,  Prodromo  di  un  opera  da  imprimersi  sopra  le  repro- 
duzione  atiimali,  8vo,  Modena,  pp.  I02,  1768,  (French  translation  by  de  la 
Sabionne,  Geneva,  1768.  English  translation.  Aft  Essay  on  Anijnal  Repro- 
atictions,  8vo,  London,  1769,  pp.  86.  The  "  Prodromo "  has  been  repub- 
lished in  volume  four  of  Spallanzani's  Opcre  Scelte.) 


REGENERATION  AND  DEATH 


199 


suffice  to  indicate  to  you  the  nature  and  process  of 
regeneration. 

We  have  many  kinds  of  regeneration  ;  we  may 
have  that  of  the  single  cell  Or  that  of  the  whole 
organism.  Let  us  consider  first  unicellular  regener- 
ation, and  accordingly  we  pass  to  the  examination  of 


B 


Fig.  67.      Stentor. 


the  next  of  our  slides,  which  represents  a  creature  of 
the  kind  called  Stentor,  Fig.  67.  It  is  a  single  cell. 
The  nucleus  of  the  cell  has  a  singular  form,  for  it  con- 
sists of  nine  bead-like  enlargements,  with  the  parts 
between    constricted    to    mere    delicate    connecting 


200  AGE,  GROWTH,  AND  DEATH 

threads  ;  its  protoplasmic  body  is  large,  and  some- 
thing of  its  structure  I  have  told  you  in  a  previous 
lecture.  A  German  investigator,  Professor  Gruber, 
has  succeeded  in  dividing  one  of  these  Sten- 
tors,  a  unicellular  creature,  animalcule,  common  in 
fresh  water,  into  three  parts,  in  such  a  method  of 
cutting  as  is  illustrated  by  the  figure  on  the  left. 
Each  of  the  three  parts  restored  itself  and  became  a 
complete  Stentor.  In  such  experiments  the  proto- 
plasm around  the  nucleus  begins  to  grow  ;  gradually 
the  original  form  is  again  assumed  ;  the  creature 
grows  larger  and  larger,  until  each  piece  acquires 
the  parent  size,  and,  so  far  as  we  can  see  with 
the  ordinary  microscopic  examination,  identically  the 
parental  structure.  That  which  was  lost  has  been 
regenerated.  We  learn,  then,  that  regeneration  is 
a  faculty  which  a  single  cell,  a  single  unit,  may 
possess. 

Another  example  of  unicellular  regeneration  is  of- 
fered us  by  nerve  fibres.  A  nerve  fibre  is  a  thread- 
like prolongation  of  a  nerve  cell  (neurone)  and  is  of 
course  a  part  of  the  cell,  as  much  so  as  the  proto- 
plasmic body  immediately  surrounding  the  nucleus. 
When  a  nerve  is  cut  across,  as  happens,  for  instance, 
necessarily  in  every  surgical  operation,  the  nerve  fi- 
bres are  severed.  The  part  which  is  separated  from 
the  central  cell  dies  by  a  degenerative  process,  the 
part  which  is  connected  with  the  cell,  on  the  contrary, 
may  grow  and  elongate  itself.  In  other  words,  the 
cell  regenerates  the  part  which  it  lost,  just  as  a  sala- 


REGENERATION  AND  DEATH  201 

mander  may  regenerate  its  lost  tail.  By  the  growth 
of  nerve  fibres  a  whole  nerve  may  be  regenerated,  a 
fact  which  is  often  of  the  utmost  practical  medical  and 
surgical  importance.  Many  researches  upon  the  re- 
generation of  nerves  have  been  made,  and  some 
questions  about  it  are  still  subject  to  dispute,  but  I 
have  confined  myself  to  such  statements  as  seem  to 
me  beyond  controversy. 

Our  next  picture  demonstrates  a  similar  phenom- 
enon. It  represents  muscle  fibres  which  have  been 
injured.  Every  muscle  fibre  contains  in  its  interior 
its  contractile  substance,  the  fibrils,  in  regard  to  which 
I  have  already  spoken  to  you  ;  but  it  also  contains  a 
certain  amount  of  substance  which  is  still  undiffer- 
entiated protoplasm.  Now  when  a  muscle  fibre  of 
this  sort  is  injured,  we  find  that  the  muscular  struc- 
ture, properly  so-called,  will  in  many  cases  quite 
disappear,  but  then  the  protoplasmic  material,  which 
is  the  undifferentiated  substance,  will  begin  to  grow 
and  the  nuclei  will  begin  to  multiply,  a,  b.  This  may 
happen  at  the  end  of  a  muscle  fibre — e,  f- — producing 
there  a  considerable  mass  of  protoplasm,  with  nuclei 
multiplying  in  it ;  or  we  may  find  a  chain  of  nuclei, 
each  with  its  separate  protoplasmic  body,  b ;  such 
nuclei  will  multiply.  When  the  increase  of  the  un- 
differentiated protoplasm  has  gone  on  far  enough,  the 
injured  muscle  will  produce  again  the  muscular  sub- 
stance proper — the  contractile  fibrils.  Muscular  fibre, 
in  other  words,  can  be  regenerated  by  itself,  but  only 
by  the  growth  of    its  undifferentiated    portion ;   the 


202 


AGE,  GROWTH,  AND  DEATH 


fibrillated  or  differentiated  portion  of  a  muscular  fibre 
has  no  regenerative  power. ^ 

Let  us  re-examine  another  figure,  Fig.  69.  Here 
is  represented  the  lining  layer  of  the  oesophagus  with 
the  cells  composing  it,  the  upper  ones  being  horny, 


Fig.  68.  Striated  Muscle  Fibres  in  Process  of  Regeneration. 
a,  b,  three  days  after  rupture  of  the  muscle;  c,  eight  days  after  rupture; 
d,  26  days;  ^,  lo  days;/,  21  days;^,  43  days.  — After  Ernst  Ziegler.  X  35° 
diameters. 

the  lower  ones  those  which  are  capable  of  active 
growth.  We  are  rather  dull.  We  do  not  often  stop 
to  think  about  things.     We  buy  a  new  horse  which 

1  The  regeneration  of  muscle  fibres  has  been  studied  hitherto  mainly  by 
pathologists,  for  in  the  higher  animals  muscular  regeneration  occurs  chiefly  as 
the  sequel  of  injury  to  the  muscle  fibres,  injury  either  mechanical  or  from  path- 
ological causes,  as,  for  example,  in  abdominal  typhus.        The  literature  of  the 


REGENERATION  AND  DEATH 


203 


comes  from  the  country  and  has  never  seen  a  train  ; 
drive  him  to  the  station,  and  are  frightened,  perhaps, 
because  the  horse  himself  is  so  much  alarmed — pos- 
sibly have  a  narrow  escape  because  of  the  excitement 


<3 


CD 


<S^~' 


(F 


^'j  tv) 


®/ 


Fig.  6g.     Section  of  the  Epithelial  Lining  of  the  Human 
(Esophagus. 

which  his  first  sight  of  a  train  causes  him.     But  the 
same  horse,  after  a  few  months'  discipline,  will  scarcely 


subject  is  quite  extensive;  nearly  sixty  articles  are  known  to  me.     I  select  the 
following,  by  consulting  which  access  to  the  remaining  literature  may  be  had  : 
W.  Waldeyer,  "  Ueber  die  Veranderungderquergestreiften  Muskelfasern  bei 
der  Entzundung  und  beim  Typhusprocess,  sowie  ueber  die  Regeneration  der- 
selben   bei   Substanzdefekten,"      Vir chow's  ArcJiiv    f.    Pathol.,   xxxiv     473 
1865. 


204  AGE.  GROWTH,  AND  DEATH 

turn  his  ear,  much  less  his  head,  to  inspect  the  train 
which  a  short  time  before  so  frightened  him  and  held 
his  attention  that  nothinof  else  could  Pfet  into  his 
mind  save  the  fright  the  train  gave  him.  So  we,  too, 
act  a  eood  deal  like  the  horse.  We  see  a  thingr  the 
first  time  and  it  surprises  us;  the  next  time  it  seems 
like  an  old  acquaintance,  a  thing  familiar  and  there- 
fore unregarded.  I  say  this  apropos  of  the  skin. 
How  many  of  you  have  thought  what  the  lesson  of 
the  skin  is  in  regard  to  the  power  of  growth?  Spring 
is  coming ;  we  shall  soon  be  taking  to  our  boats,  row- 
ing or  canoeing,  and  the  first  day  we  do  so  doubtless 
we  shall  have  blisters  upon  our  hands,  and  the  outer 
part  of  the  skin,  raised  by  the  blister,  will  probably 
fall  oi'f  and  be  lost  altogether.  The  softer  underlying 
skin  will  be  exposed,  will  be  sensitive  and  uncomfort- 
able for  a  while,  but  soon  the  cells  behind  the  surface 
will  assume  a  horny  character,  the  cells  underneath 
will  grow  and  multiply,  and  presently  the  wound  will 
be  healed  over.  Did  you  ever  stop  to  think  that 
that  means  that  there  is  a  reserve  power  of  growth  in 


p.  Fraisse,  Die  Regeneration  von  Geweben  und  Organen  bei  den  Wirbel- 
thieren,  Berlin,  1885. 

Nauwerck,   Uebcr  Rluskelregeneration  nach  Verletzungen,  Jena,  i8go. 

R.  Volkmann,  "  Ueber  die  Regeneration  des  quergestreiften  Muskelgewebes 
beim  Menschen  und  Saugethier,"  Ziegle7-'s  Beitrdge  Pathol.,  xii.,  233,  1893. 

E.  Ziegler,  "  Ueber  die  Reparation  verletzter  Gewebe,"  Z>f«/j(r^^»«^a^.  Woch- 
enschri/t,  1900,  p.  783. 

Alex.  Schmincke,  "Die  Regeneration  der  quergestreiften  Muskelfasern  bei 
den  Wirbelthieren.  Einevergleichendpathologische  Studie.  I.  Ichthyopsiden," 
Verhandl.  Fhys.-tned.  GesellscJiaft  Wfirzbiirg,  N.  A,xxxix.,  15-130,  Tafel  1., 
II.     (Gives  an  exhaustive  review  of  previous  investigations.) 


REGENERATION  AND  DEATH  205 

the  skin  all  the  time  ?  always  ready  to  act,  to  come 
forward,  waiting  only  for  the  chance,  and  that  there  is 
besides  something  which  keeps  it  in,  which  holds  it 
back,  which  stops  it  ?  We  call  this  stopping  physio- 
logical function — inhibition  ;  we  say  that  the  growth 
of  the  skin  is  inhibited  ;  though  in  the  deep  part  of 
the  skin  all  the  time  there  are  the  cells  ready  to  grow 
as  soon  as  that  power  of  inhibition  is  taken  away,  while 
it  is  active  they  will  not  grow.  The  simple  blister 
tells  us  all  that.  There  is,  then,  a  power  of  regulation 
which  expresses  itself  in  this  inhibitory  effect.  When 
a  salamander  has  its  tail  cut  off  by  the  experimenter 
and  the  new  tail  grows,  just  enough  is  produced.  The 
new  tail  is  like  the  old.  The  tissues  grow  out  until 
the  volume  of  that  which  is  lost  is  replaced,  and  then 
they  stop.  But  if  the  tail  should  be  cut  off  again,  re- 
generation would  occur  again.  The  experiments  may 
be  repeated  many  times  over.  It  indicates  to  us  that 
always  the  growing  power  is  there,  but  it  is  held  in 
check.  What  that  check  may  be  is  one  of  the  great 
discoveries  we  are  now  longing  for.  The  discovery, 
when  made,  is  likely  to  prove  of  great  practical  im- 
portance. The  phenomenon  of  things  escaping  from 
inhibitory  control  and  overgrowing  is  familiar.  Such 
escapes  we  encounter  in  tumors,  cancers,  sarcoma, 
and  various  other  abnormal  forms  of  growth  that  occur 
in  the  body.i     They  are  due  to  the  inherent  growth 

1  A  semi-popular  exposition  of  this  view  regarding  malignant  tumors  has  been 
published  by  V.  Dungern  and  R.  Werner,  Das  Wesen  de?-  bosartigeti  Gesch- 
willste.     Eine  biologische  Studie,  8vo.  pp.  159,  Leipzig,  1907. 


2o6  AGE,  GROWTH,  AND  DEATH 

power  of  cells  kept  more  or  less  in  the  young  type, 
which  for  some  reason  have  got  beyond  the  control 
of  the  inhibitory  force,  the  regulatory  power  which 
ordinarily  keeps  them  in.  No  picture  of  the  growth 
or  development  of  the  living  animal  would  be  com- 
plete if  it  confined  its  attention  only  to  the  power  of 
growth  in  relation  to  cytomorphosis.  It  must  also  in- 
clude the  contemplation  and  study  of  the  regulatory 
power  of  the  organs.  Experiments  are  being  made  in 
many  places,  minds  are  at  work  in  many  laboratories 
upon  this  problem  of  the  regulation  of  structure  and 
growth.  Much  is  to  be  hoped  from  such  researches; 
not  merely  insight  into  the  normal  development,  but 
insight  also  into  the  abnormal.  Nothing,  perhaps,  is 
more  to  be  desired  at  the  present  time  than  that  we 
should  solve  the  mystery  of  the  regulatory  power  which 
presides  over  growth.  It  would  be  of  immense  medical 
importance.  Could  we  understand  it,  and  could  we 
from  our  understanding  derive  some  practical  applica- 
tion of  our  scientific  discoveries  in  this  field, — in  other 
words,  could  we  learn  to  regulate  the  formation  and" 
growth  of  tumors, — we  should  say  of  it  justly  that  it 
was  as  noteworthy  a  contribution  to  medical  know- 
ledge as  the  discovery  of  the  germs  of  disease,  and 
would  doubtless  prove  equally  beneficial  to  mankind. 
Although,  then,  the  .'tudy  which  I  have  been  laying 
before  you  must  necessarily  seem  in  many  respects 
abstruse  and  far  away  from  practical  applications,  we 
learn  that  it  is  not  really  so,  and  that  it  leads  by  no 
very  remote  path  to  the  consideration  of  problems 


REGENERATION  AND  DEATH  207 

the   useful    applications    of    which    are    immediately 
obvious  to  every  one. 

We  find  in  the  process  of  regeneration  of  organs 
or  parts  of  the  body  that  it  is  always  the  young  cell 
which  plays  the  principal  part.  This  is  beautifully 
illustrated  in  the  picture  upon  the  screen,  Fig.  70. 
There  is  a  little  creature,  which  many  of  you  have 
seen  in  the  garden,  consisting  of  joints,  which  rolls 
itself  up  into  a  little  ball,  and  therefore  is  often  called 
the  "  pill-bug."  It  is  not,  however,  an  insect  or  a  bug, 
properly  so-called,  but  belongs  to  a  family  of  crusta- 
ceans. It  has  on  its  head  a  little  feeler  which  we 
call  the  antenna.  The  particular  kind  of  arthropod, 
the  antenna  of  which  has  been  studied  and  drawings 
of  it  made  to  furnish  us  this  plate,  is  known  by  the 
name  of  Oniscus.  In  his  researches  the  experimenter. 
Dr.  Ost,^  cut  off  the  antenna  in  the  middle  of  a  joint 
and  found  that  it  rapidly  healed  over.  Here  are  pic- 
tured the  stages  of  the  progressive  restoration.  Part 
of  the  antenna  has  been  cut  off  in  this  case ;  the  wound 
was  healed  over  here,  No.  i,  a,  the  new  tissue  has 
begun  to  grow.  No.  2,  b,  and  the  cells  at  this  point 
are  very  simple  in  character.  They  spread  out  and 
grow,  and  then,  within  the  interior  of  the  hard  shell  of 
the  feeler,  a  retraction  of  the  substance  occurs,  and 
the  new  growing  cells  within  this  space  gradually  be- 
gin to  shape  themselves  out.  No.  3,  b,  and  we  see 
presently  an  accumulation  of  cells  which  is  assuming 

1  Ost,  T-.  "  Zur  Kenntniss  der  Regeneration  der  Extremitaten  bei  den  Arthro- 
poden,"  Archiv  f.  Entwickehtn^smechanik,  xxii.,  289-324,  pis.  x-xii. 


Fig.  70.  Longitudinal  Sections  through  the  An- 
tenna OF  Oniscus  IN  Various  Stages  of  Regeneration 
AFTER  Amputation. — After  Ost. 

a,  cicatricial  tissue ;  b,  regenerated  tissue  ;  cu,  cuticula,  or 
outer  shell ;  gl,  glands  ;  pig,  pigment.     Magnified. 


208 


REGENERATION  AND  DEATH 


209 


a  definite  form,  No.  4,  d,  that  in  the  next  figure  has 
clearly  become  the  promise 
or  beginning  of  a  new  ter- 
minal joint,  Fig.  71,  which 
will  become  free  when  at  the 
next  moult  the  old  shell 
or  cuticle  is  cast  off.  The 
minute  study  of  this  process 
has  shown  that  the  regenera- 
tion depends  practically  ex- 
clusively upon  the  cells  of  the 
young  type,  and  that  after 
they  have  grown  out  and  ac- 
cumulated here  in  this  man- 
ner, No.  3,  d,  some  of  them 
undergo  differentiation,  be- 
coming muscle  cells ;  others 
change  in  the  manner  indi- 
cated here,  No.  4,  where  we 
see  a  commencing  alteration 
of  the  nuclei,  which  is  further 
accented  in  Fig.  71,  and  leads 

,  .  r    ,  11  Fig.  71.     Section  through 

to  such  a  groupmg  of  the  cells    ^  regenerating  antenna  of 

that    the    glands,    which    were      C«?V<r«J.— After  Ost.     Advanced 

originally  present  there,  are    stage,  in  which  the  young  new 

^            "'     ^  joint  IS  already  shaped  within  the 

also  reproduced.      The  regen-  old  shell,    a,  cicatricial  tissue  ;  d, 

erative    process,    then,   clearly  regenerated  tissue  ;  y.  new  joint ; 

,,,                                       f.                        .  c«,cuticula (old  shell).  Magnified. 

illustrates  to  us,  irom  another 

point  of  view,    the   great  importance   of  the  young 

type  of  cells. 


2IO  AGE,  GROWTH,  AND  DEATH 

The  eyes  of  crabs  and  related  animals  {Decapoda) 
are  born  on  stalks.  If  these  stalks  are  cut  partly  off  so 
as  to  remove  all  of  the  eye,  but  leave  part  of  the 
nervous  centre  (^ganglion)  in  the  base  of  the  stalk, 
it  is  found  that  in  a  considerable  percentage  of  cases  a 
new  eye  will  be  formed.  Miss  M.  I.  Steele^  has  made 
a  study  of  this  regeneration.  She  states  that  the 
healing  over  of  the  wound  and  the  growth  of  the 
undifferentiated  cells  of  the  outer  layer  (ectoderm 
or  hypodermis)  occurs  much  as  just  described  for 
the  antenna  of  Oniscus.  Later  the  hypodermal  cells 
lose  their  primitive  and  simple  character  and  by 
passing  through  various  but  co-ordinated  differen- 
tiations evolve  new  complete  ommatidia^  as  the 
structural  units  are  termed  which  constitute  the  eye 
in  crabs  and  other  Crustacea.  It  may  interest  you  to 
know  that  if  the  whole  or  nearly  the  whole  eye-stalk 
be  cut  off,  regeneration  may  still  take  place,  but  if  it 
does  a  feeler-like  appendage  or  antenna  results,  with- 
out any  special  optic  apparatus.  This  singular  phe- 
nomenon was  first  observed  by  Professor  Herbst.2 

One  of  the  interesting  illustrations  of  the  import- 
ance of  undifferentiated  cells  is  afforded,  according  to 
recent  observations,  by  certain  worms  of  lowly  organ- 
isation, known  as  planarians.  The  space  between  the 
organs  of  one  of  these  animals  is  occupied  by  a  low 
form  of  connective  tissue, — a  syncytium  termed  the 

>  Mary  Isabelle  Steele,  "  Regeneration  in  Compound  Eyes  of  Crustacea," 
Jour.  Exp.  ZooL,  v.,  163-244,  16  pis.  (1907). 

2  C.  Herbst,  Ai-ch.  f.  Entwickelungsmechanik,  ii.,  455-516(1896).  See  also 
Bd.  ix.,  215-293  (1900). 


REGENERATION  AND  DEATH  211 

mesenchyma, — scattered  about  in  which  are  free  sim- 
ple cells, ^  which  are  referred  to  by  recent  authors  as 
"parenchymal"  or  "formative"  cells.  Now  if  the 
head  or  tail  of  a  planarian  be  cut  off,  the  part  lost  is 
regenerated.  The  regeneration  is  effected  not  by  the 
growth  of  the  old  tissues,  each  producing  of  its  own 
kind,  but  chiefly  (perhaps  wholly)  by  the  multiplica- 
tion and  differentiation  of  the  "  formative  "  cells  which, 
after  migrating  to  where  they  are  needed,  produce 
outer  skin  (epidermis),  intestine,  muscle,  etc.  They 
constitute  a  store  of  undifferentiated  cells,  ready  to 
enter  upon  various  active  differentiations  when  occa- 
sion arises. 

There  is  a  marine  animal  called  Ciona  :  it  belonofs 
to  the  class  of  the  Ascidians.  Professor  Jacques  Loeb  2 
discovered  in  1892  that  if  the  portion  of  the  animal 
containing  the  nerve  ganglion,  or  rudimentary  brain, 
be  cut  out,  it  will  be  regenerated,  and  a  new  brain 
formed.  This  discovery  was  confirmed  by  Pio  Min- 
gazzini,^  a  gifted  Italian  zoologist  whose  early  death 
we  lament.      Recently,   L.    S.   Schultze  *  has   shown 

'  So  far  as  known  to  me  these  ceils  were  first  described  by  H.  N.  Moseley 
("  On  the  Anatomy  and  Histology  of  the  Landplanarians  of  Ceylon."  Philos. 
Transactions,  1874,  p.  105).  J.  Keller  in  1894  {Jeua'ische  Zeiischr.  f.  Natur- 
wiss.,  xxvii,,  371-407)  demonstrated  their  role  in  regeneration,  Keller's  inter- 
pretation has  been  confirmed  by  W.  C.  Curtis  (/"rt^r.  Boston  Soc.  Nat.  History, 
XXX.,  pp.  515-559)  and  Miss  N.  M.  Stevens  {.4rc/i.  f.  Entwickehingsme- 
chanik,  xxiv.,  350-373,  IQ07).  The  cells  are  of  the  embryonic  type,  that  is  to 
say,  without  any  specialisation  or  differentiation. 

^J.  Loeb,   Untersuchungen  zur  Physiologischen  Morphologic,  1891—92. 

^  P.  Mingazzini,  "Sulla  regenerazione  nei  tunicati,"  Boll.  Soc.  Natur- 
alisti,  Napoli,  v.  (1891.) 

4  L.  S.  Schultze,  "  Die  Regeneration  des  Ganglions  bei  Ciona  intestinalis,  L., 


212  AGE,  GROWTH,  AND  DEATH 

that  the  regeneration  is  accomplished  by  the  growth 
of  undifferentiated  cells,  which  subsequently  undergo 
differentiation. 

The  cases  of  regeneration  which  we  have  re- 
viewed are  all  connected  with  the  repair  of  injuries. 
But  there  are  also  cases  known  of  spontaneous  and 
normal  regeneration,  as  they  might  be  called.  For 
example,  there  are  certain  fresh-water  jointed  worms, 
annelids,  which  produce  in  the  midst  of  their  body 
from  time  to  time  a  budding  zone,  a  narrow  band  of 
tissue  intervening  between  two  segments.  The  ante- 
rior part  of  the  zone  forms  a  new  tail  for  the  anterior 
part  of  the  worm,  the  posterior  part  of  the  zone 
forms  a  new  head  for  the  posterior  part  of  the  worm  ; 
division  follows,  and  thus  out  of  one  worm  two  are 
produced.  The  external  features  of  this  wonderful 
process  were  described  very  well  indeed  in  1771,  by 
the  celebrated  naturalist  O.  F.  Mullen^  It  was  re- 
served for  Carl  Semper,^  under  whom  I  had  the  hon- 
our to  study  in  1875-76,  to  demonstrate,  at  that  very 
date,  that  the  cells  of  the  budding  zone  are  of  the 
embryonic  type,  and  that  after  having  multiplied 
sufficiently  they  begin  to  differentiate  into  the  tissues 

und  iiberdas  Verhaltniss  der  Regeneration  und  der  Knospung  zur  Keimblatt- 
lelire,"  Jena  Hsche  Zeiischrift,  xxxiii.,  263-344,  Taf.  XII.,  XIII.  (1899).  For 
our  present  purposes  it  is  a  matter  of  regret  that  on  the  cytological  side 
Schultze's  observations  leave  much  to  be  desired. 

'  O.  F.  Miiller,  Naturgeschichte  einiger  Wurmarten  des  siissen  tmd  salzigen 
Wassers,  Kopenhagen,  1771. 

^  Carl  Semper,  "  Die  Verwandschaften  der  gegliederten  Thiere,  III."  Sem- 
per's  Arbeiten,  Zool.  Zootom.  Inst.  Wiirzburg,  iii.,  115.  See  especially 
p.  ibiff. 


REGENERATION  AND  DEATH  213 

necessary  to  complete  the  new  tail  and  the  new  head. 
Through  Professor  Semper's  kindness  I  had  the 
privilege  of  seeing  many  of  his  preparations,  and  can 
therefore  speak  with  confidence  about  his  results. 

This  completes  the  evidence  which  my  time  per- 
mits me  to  lay  before  you  in  order  to  convince  you 
that  the  young  type  of  cells  really  is  physiologically 
and  functionally  important,  that  it  really  does  possess 
the  power  of  growth  that  I  have  attributed  to  it. 

We  will  pass  now  to  another  part  of  our  subject, 
with  which  the  lecture  will  close.  Age  represents  the 
result  of  a  progressive  cytomorphosis.  We  have 
learned  that  of  cytomorphosis  death  is  the  end,  the 
culmination.  It  is  a  necessary  result  of  the  modifica- 
tion and  change  of  structure  which  goes  on  in  every 
individual  of  our  species  and  of  all  the  higher  ani- 
mals. We  are  familiar  with  the  death  of  cells.  It 
occurs  constantly  and,  as  I  have  endeavoured  to  ex- 
plain to  you,  it  plays  a  great  part  in  life.  It  promotes 
the  performance  of  various  functions  which  are  of 
advantage  to  the  body  as  a  whole,  which  could  not 
be  accomplished  without  the  death  of  some  cells. 
But  the  death  which  we  have  in  mind  when  we  speak 
ordinarily  of  death  is  something  different  from  this. 
It  is  the  death  of  the  whole.  But  even  the  death  of 
the  whole  has  its  strange  complications.  A  great 
deal  of  our  knowledge  of  the  functioning  of  the  body 
is  due  to  the  fact  that  the  parts  do  not  die  when,  as 
we  commonly  say,  the  body  as  a  whole,  the  indi- 
vidual, is  dead.     The  organ  is  alive  and  well,     One 


214  AGE,  GROWTH,  AND  DEATH 

of  the  most  impressive  sights  which  I  have  ever 
seen  has  been  the  sight  of  the  heart  of  a  quadruped, 
a  dog,  continuing  to  beat  after  it  had  been  taken  out 
from  the  body.  The  dog  was  dead — the  rest  of  the 
body  was  dead — but  the  heart  lay  upon  the  physio- 
logist's table,  beating.  The  experimenter  could  sup- 
ply it  with  the  necessary  circulation.  He  could  give 
stimuli  to  it,  and  under  these  favourable  conditions 
make  important  discoveries  in  regard  to  the  function- 
ing of  the  heart.  So,  too,  I  myself  made  experiments 
upon  a  muscle  once  part  of  a  living  dog,  separated 
entirely  from  the  parent  body,  supplied  with  its  own 
artificial  circulation,  and  from  those  experiments  was 
able  to  discover  some  new  unexpected  results  in  re- 
gard to  the  nutrition  of  the  muscle,  and  the  changes 
which  chemically  go  on  in  it.^  This  over-living,  then, 
of  the  parts  of  the  body,  their  separate  life,  is  some- 
thing which  we  must  familiarise  ourselves  with,  and 
the  great  importance  of  which  we  must  carefully  ac- 
knowledge, for  much  of  the  benefit  which  the  medi- 
cal  practitioner  is  able  to  render  to  us  and  to  our 
friends  to-day  is  due  to  the  knowledge  which  has  been 
derived  experimentally  from  the  study  of  the  over- 
living or  surviving  parts  of  a  body  which  as  a  whole 
was  dead. 

Death    is  not  a  universal  accompaniment  of  life. 
In    many    of  the    lower  organisms    death    does  not 

^Charles  S.  Minot,  "Die  Bildung  der  Kohlensaure  innerhalb  des  ruhenden 
und  erregten  Muskels,"  Ludwig's  Arbeiten  der  Physiol.  Anstalt,  Leipzig, 
xi.,  1-24  (1876). 


REGENERATION  AND  DEATH  215 

occur,  so  far  as  we  at  present  know,  as  a  natural  and 
necessary  result  of  life.  Death  with  them  is  purely 
the  result  of  an  accident,  some  external  cause.  Our 
existing  science  leads  us  therefore  to  the  conception 
that  natural  death  has  been  acquired  during  the  pro- 
cess of  evolution  of  living  organisms.^  Why  should 
it  have  been  acquired  ?  You  will,  I  think,  readily 
answer  this  question,  if  you  hold  that  the  views  which 
I  have  been  bringing  before  you  have  been  well  de- 
fended, by  saying  that  it  is  due  to  differentiation, 2 
that  when  the  cells  acquire  the  additional  faculty  of 
passing  beyond  the  simple  stage  to  the  more  com- 
plicated organisation,  they  lose  some  of  their  vital- 
ity, some  of  their  power  of  growth,  some  of  their 
possibilities  of  perpetuation  ;  and  as  the  organisation 
in  the  process  of  evolution  becomes  higher  and 
higher,  the  necessity  for  change  becomes  more  and 
more  imperative.  But  it  involves  the  end.  Differen- 
tiation leads  up,  as  its  inevitable  conclusion,  to  death. 
Death  is  the  price  we  are  obliged  to  pay  for  our 
organisation,  for  the  differentiation  which  exists  in  us. 
Is  it  too  high  a  price  ?  To  that  organisation  we  are 
indebted  for  the  great  array  of  faculties  with  which 
we  are  endowed.  To  it  we  are  indebted  for  the 
means  of  appreciating  the  sort  of  world,  the  kind  of 
universe,  in  which  we  are  placed.     To  it  we  are  in- 


1  On  death  among  Protozoa  see  Appendix  No.  III. 

2  The  theory  that  natural  death  is  the  incidental  result  of  cellular  differentia- 
tion was  first  put  forward  by  me  in  1885  ;  compare  Proceedings  American 
Association  Adv.  Science,  vol.  xxxiv.,  p.  311. 


2i6  AGE,  GROWTH,  AND  DEATH 

debted  for  all  the  conveniences  of  existence,  by  which 
we  are  able  to  carry  on  our  physiological  processes 
in  a  far  better  and  more  comfortable  manner  than 
can  the  lower  forms  of  life.  To  it  we  are  indebted 
for  the  possibility  of  those  human  relations  which 
are  among  the  most  precious  parts  of  our  experience. 
And  we  are  indebted  to  it  also  for  the  possibility  of 
the  higher  spiritual  emotions.  All  this  is  what  we 
have  bought  at  the  price  of  death,  and  it  does  not 
seem  to  me  too  much  for  us  to  pay.  We  would  not, 
I  think,  any  of  us,  wish  to  go  back  to  the  condition  of 
the  lowly  organism,  which  might  perpetuate  its  own 
kind  and  suffer  death  only  as  a  result  of  accident,  in 
order  that  we  might  live  on  this  earth  perpetually; 
we  would  not  think  of  it  for  a  moment.  We  accept 
the  price.  Death  of  the  whole  comes,  as  we  now 
know,  whenever  some  essential  part  of  the  body 
gives  way. — sometimes  one,  sometimes  another  ;  per- 
haps the  brain,  perhaps  the  heart,  perhaps  one  of 
the  other  internal  organs  may  be  the  first  in  which 
the  change  of  cytomorphosis  goes  so  far  that  it  can 
no  longer  perform  its  share  of  work  and,  failing, 
brings  about  the  failure  of  the  whole.  This  is  the 
scientific  view  of  death.  It  leaves  death  with  all  its 
mystery,  with  all  its  sacredness  ;  we  are  not  in  the 
least  able  at  the  present  time  to  say  what  life  is,  still 
less,  perhaps,  what  death  is.  We  say  of  certain 
things — they  are  alive  ;  of  certain  others — they  are 
dead ;  but  what  the  difference  may  be,  what  is  essen- 
tial to  those  two  states,  science  is  utterly  unable  to 


REGENERATION  AND  DEATH  217 

tell  us  at  the  present  time.  It  is  a  phenomenon 
with  which  we  are  so  familiar  that  perhaps  we  do 
not  think  enough  about  it. 

In  the  next  lecture  there  will  be  some  other  gen- 
eral aspects  of  our  subject  to  present  to  you,  and  a 
formulation  of  the  general  conclusions  toward  which 
all  the  lectures  have  aimed. 


VI 

THE    FOUR    LAWS    OF    AGE 

T  ADIES  AND  GENTLEMEN:  I  have  re- 
ferred in  these  lectures  repeatedly  to  the  cell 
and  its  two  component  parts,  the  nucleus  and  the 
protoplasm.  To-night  I  shall  have  only  a  few  refer- 
ences to  make  directly  to  these,  and  shall  pass  on  for 
the  latter  part  of  the  hour  to  another  class  of  con- 
siderations bearing  upon  the  problem  of  age.  Before 
we  turn  to  these  new  considerations,  however,  I  wish 
to  say  a  few  words  by  way  of  recapitulation  concern- 
ing the  changes  in  the  cells  as  corresponding  to  age. 
Cells,  as  you  know  from  what  I  have  told  you,  un- 
dergo in  the  body  for  the  greater  part  a  progressive 
change  which  we  call  their  differentiation.  We  may 
say  that  there  are  four  kinds  of  cells  for  purposes  of 
an  elementary  classification  to  be  used  in  a  simple  ex- 
position like  the  present.  The  first  kind  are  those 
cells  of  the  young  type,  in  which  the  protoplasm  is 
simple,  and  shows  as  yet  no  trace  of  differentiation. 
These  cells  are  capable  of  rapid  multiplication,  and 
some  of  them  are  found  still  persisting  in  various 
parts  of  the  adult  body,  and  serve  to  maintain  the 
growth  of  the  body  in   its  mature  stage.     Another 

218 


THE  FOUR  LAWS  OF  AGE  219 

class  of  cells  presents  to  us  the  curious  spectacle  of  a 
partial  differentiation ;  such  are  the  muscle  fibres 
by  which  we  accomplish  our  voluntary  movements. 
These  fibres  consisted  originally  only  of  protoplasm 
with  the  appropriate  nuclei,  but,  as  they  are  differen- 
tiated, part  of  the  protoplasm  changes  into  contractile 
substance.  Another  part  remains  pure  protoplasm 
unaltered.  If  now  the  muscular  or  contractile  por- 
tion of  the  fibre  be  destroyed,  the  undifferentiated 
part  of  the  protoplasm  then  shows  that  it  has  still  the 
power  of  growth.  It  has  only  been  held  back  by  the 
condition  of  organisation,  and  we  perceive  in  the  re- 
generation of  these  fibres  evidence  of  the  fact  that  so 
long  as  the  protoplasm  is  undifferentiated  it  has  the 
power  of  growth,  which,  however,  does  not  reveal 
itself  unless  an  opportunity  is  afforded.  Third,  we 
come  to  the  cells  which  are  moderately  differentiated  ; 
such,  for  instance,  are  the  cells  of  the  liver,  and  if 
for  any  reason  a  portion  of  the  liver  be  injured  by  ac- 
cident or  disease,  we  find  that  these  partially  differen- 
tiated cells  reveal  at  once  that  they  have  a  limited 
power  of  growth  still  left.  If  we  pass  on  to  the 
fourth  class,  that  in  which  differentiation  is  carried  to 
the  highest  extreme,  we  find  that  the  cells  do  not 
have  the  power  of  multiplication.  Such  are  the  nerve 
cells  by  which  the  higher  functions  of  the  body  are 
carried  on.  They  represent  the  extreme  of  cellular 
differentiation,  and  almost  never  do  we  see  these 
cells  multiplying  after  the  differentiation  is  accom- 
plished.   Presented  in  this  form,  we  then  recognise,  it 


220 


AGE,  GROWTH,  AND  DEATH 


seems  to  me  clearly,  the  effect  of  differentiation  upon 
the  growth  of  cells.  The  facts  are  clear  as  to  their 
meaning-. 

We  can,  however,  proceed  a  little  farther  than  this, 

/  -—- because  we  can  actually  ascertain, 

(  >^-v  ...  '  ]  approximately  at  least,  the  rate  at 
')  ?^-  '-'  ^  ^  which  cells  multiply.  We  accom- 
I  plish  this  by  determining  the  '?m- 
j^  '  totic  index.  The  mitotic  index  is 
the  number  of  cells  to  be  found  at 
any  given  moment  in  the  active 
'^      j     process  of  division  out  of  a  total 


of  one  thousand  cells. 
■""^  May  I  pause  a  moment  to  recall 

Fig   72.     Portion  of    this  picture  to  you  and  ask  you  to 

THE  Outer  Wall  of  a  ,  ^  ,    -^       .  -'     . 

Primitive     Muscular    notice     at    this    point    the    CUrious 

Segment  of  a  Cat   Em-      ,      ,  1  •    1 

BRY00F4.6MM.   Harvard   darker   spot   which    represents   a 
fet7t,rk«?"ro":    nucleus    in   process   of   division? 

The  resting  nuclei  are  oval.     YoU  wiU   See    it  WOuld    be    easV    in 

pale,    and    granular.      i  he  _  •' 

dividing  or  mitotic  nuclei,    such  a  preparation  as  this  to  count 

of  which   there  are  ttixee,        .,  ,    .  .  .. 

are  dark,  irregular  in  out-     the    UUClei     One    by    One    UUtll    One 

line,  and  ghow  the  chromo-     ij  ,  .  ,1  i         1. 

somes.     In  this  case  the    had  got  up  to  a  thousand,  and  to 
dividing  nuclei  all  lie  near    record,  as    oueweut   alouP",   how 

the    inner   surface    01     the  '  &' 

wall.     The  picture  iiius-    many  of  the  nuclei  are  in  process 

trates  the  ease  with  which         ...... 

mitotic  figures  may  be  re-     of  dlVlSlOU,   for  the    nucleus    m    dl- 
cognised.  ...  .-,  .        ,  r^-,  . 

Vision  IS  easily  recognised.  1  his 
process  of  division  is  named  mitosis  :  the  figure  which 
the  nucleus  presents  while  it  is  undergoing  division 
we  call  a  mitotic  figure.  Counting  the  dividing  nuclei, 
we  may  determine  that  in  a  thousand  cells  there  are  a 


THE  FOUR  LAWS  OF  AGE  221 

given  number  which  have  nuclei  in  process  of  divis- 
ion, and  such  a  number  I  propose  to  call  "  the  mitotic 
index,"-  I  wish  now  only  to  call  to  your  attention  this 
picture  because  it  enables  me  to  illustrate  before  you 
the  method  of  measurino-  the  mitotic  index. 

In  the  rabbit  embryo  at  seven  and  one  half  days,  I 
have  found  by  actual  count  that  there  are  in  the  outer 
layer  of  cells,  known  technically  as  the  ectoderm,  18 
of  these  divisions  per  thousand  ;  in  the  middle  layer, 
technically  the  mesoderm,  1 7,  and  in  the  inner  layer, 
the  entoderm,  18.  At  ten  days  we  find  the  number 
already  reduced,  and  the  figures  are,  respectively,  14, 
13,  and  15,  and  for  the  cells  of  the  blood  only  10. 
There  has  already  been  a  great  reduction.  In  the 
next  phase  of  development  (rabbit  embryo  of  thirteen 
days),  we  find,  however,  that  the  parts  are  growing 
irregularly,  some  faster,  some  slower.  We  note  that 
wherever  a  trace  of  differentiation  has  occurred,  the 
rate  of  growth  is  diminished ;  where  that  differentia- 
tion does  not  show  itself,  the  rate  of  growth  may  even 
increase  in  order  to  acquire  a  certain  special  develop- 
ment of  a  particular  part.  So  that  instead  of  uni- 
formity of  values  for  the  mitotic  index,  we  get  a  great 
variety.  But,  nevertheless,  the  general  decline  can  be 
demonstrated  by  the  figures.     In  the  spinal  cord  the 

'  Cells  are  known  to  divide  without  mitotic  figures  appearing  ;  the  process  is 
then  termed  amitosis.  Amitosis  occurs  in  certain  degenerating  cells  of  mam- 
mals and  is  said  to  occur  in  sundry  invertebrates  as  a  normal  process.  So  far  as 
I  am  aware  there  is,  however,  at  least  as  yet,  no  evidence  that  amitosis  occurs 
in  the  embryos  of  the  higher  vertebrates.  If  it  did  occur  it  might  diminish  the 
validity  of  the  mitotic  index. 


222  AGE,  GROWTH,  AND  DEATH 

index  is  ii,  in  the  general  connective  tissue  of  the 
body  lo;  for  the  cells  of  the  liver  ii;  in  the  outside 
layer  of  the  skin  lo  ;  in  the  excretory  organ  6  ;  in  the 
tissue  which  forms  the  centre  of  the  limb  also  6. 
There  has,  then,  been  a  rapid  decline  in  the  rate  of  cell 
multiplication  just  in  this  period  when  differentiation 
is  going  on.  This  is,  so  far  as  I  know,  an  entirely 
new  line  of  research.  The  counting  of  a  thousand 
cells  is  not  to  be  done  very  rapidly  ;  it  must  be  under- 
taken with  patience,  care,  and  requires  time.  It  has 
not,  I  regret  to  say,  been  possible  for  me  yet  to  ex- 
tend the  number  of  these  counts  beyond  those  I  have 
given  you,  but  it  is  safe  to  say  that  in  the  yet 
more  differentiated  state,  the  number  of  cells  in  divi- 
sion is  constantly  lessened,  and  it  is  only  a  question 
of  counting  to  determine  the  mitotic  index  accurately. 
That  there  is  a  further  diminution  beyond  that  which 
the  mitotic  indices  I  have  demonstrated  to  you  repre- 
sent is  perfectly  certain.  I  only  regret  that  I  am  not 
able  to  give  you  exact  numerical  values. 

I  wish  very  much  that  my  time  permitted  me  to 
branch  off  into  certain  topics  intimately  associated 
with  the  general  theme  we  have  been  considering 
together  on  these  successive  evenings,  but  we  can 
only  allude  to  a  few  of  these.  The  first  collateral 
subject  on  which  I  wish  to  speak  to  you  briefly  is 
that  which  we  call  the  law  of  genetic  restriction}  which 

'  C.  S.  Minot,  Laboratory  Text-book  of  Embryology  (1903),  p.  30.  This  law 
of  genetic  restriction  had  been  foreshadowed  by  M.  Nussbaum  {Arch.f.  microsk. 
Anal.,  xxvi.,  pp.  522,  524).  He  expresses  well  and  ingeniously  the  change  of 
progressive  differentiation  in  Metazoan  cells.     His  idea  is  that  each  cell  is  a 


THE  FOUR  LAWS  OF  AGE  223 

means  that  after  a  cell  has  progressed  and  is  differen- 
tiated a  certain  distance,  its  fate  is  by  so  much  deter- 
mined. It  may  from  that  pass  on,  turn  in  one  direction 
or  another,  always  progressing,  going  onward  in  its 
cytomorphosis  ;  but  the  general  direction  has  been 
prescribed,  and  the  possibilities  of  that  cell  as  it  pro- 
gresses in  its  development  become  more  and  more 
restricted.  For  instance,  the  cells  which  are  set  apart 
to  form  the  central  nervous  system  after  they  are  so 
set  apart  cannot  form  any  other  kind  of  tissue.  ^  After 
the  nervous  system  is  separated  in  the  progress  of 
development  from  the  rest  of  the  body,  its  cells  may 
become  either  nerve  cells  proper  or  supporting  cells 
(neuroglia),  which  latter  never  acquire  the  nervous 
character  proper,  but  serve  to  uphold  and  keep  in 
place  the  true  nervous  elements.  They  represent  the 
skeleton  of  the  central  nervous  system.  After  the 
^ 

"  multiplum  lebensfahiger  nnd  gestaltender  Substanz."  As  the  ovum  can  pro- 
duce two  ova,  it  can  produce  two  individuals.  Ectoderm  cells  can  produce 
more  ectoderm,  but  not  a  whole  new  individual. 

>  An  unexpected  exception  to  this  statement  has  been  discovered,  which  is, 
however,  more  apparent  than  real.  In  certain  Amphibia  it  has  been  found  that, 
if  the  lens  of  the  eye  is  extirpated  from  a  young  larva,  a  new  lens  will  be 
formed  at  the  expense  of  the  retina,  which  itself  arises  from  an  outgrowth  of 
brain  tissue.  At  the  time  the  retinal  lens  is  produced,  however,  the  retinal  cells 
are  still  in  an  undifferentiated  state,  and  those  retinal  cells  which  have  advanced 
to  the  stage  of  young  differentiated  elements  cannot  produce  a  lens.  The 
normal  lens  is  developed  from  the  outer  skin  (epidermis)  of  the  embryo.  See 
A.  Fischel,  Anato7nische  Hefte,  xiv.,  p.  i,  (1900)  and  Archiv.  f.  Entwickelungs- 
?)iech,,  XV.,  p.  i;  G.  Wolff,  Archiv,  f.  Entwickelungsmeck.,  i.,  pp.  380- 
390,  and  xii.,  pp.  307-351  ;  W.  H.  Lewis,  A?nericanyoiirnal  of  Anatomy,  iii. 
505-536,  1904.  It  is  important  to  note  that  the  retinal  lens  differs  greatly  in 
its  cell  structure  from  the  normal  lens,  and  is  smaller,  though  resembling  it  in 
general  form. 


224  AGE,  GROWTH,  AND  DEATH 

cells  of  the  nervous  system  are  separated  into  these  two 
fundamental  classes  they  cannot  change.  A  cell  form- 
ing a  part  of  the  supporting  framework  of  the  brain 
cannot  become  a  nerve  cell ;  and  a  nerve  cell  cannot 
become  a  supporting  cell.  The  destiny  of  them  be- 
comes more  and  more  fixed,  their  future  possibili- 
ties more  and  more  limited,  as  their  cytomorphosis 
goes  on. 

The  law  of  genetic  restriction  has  a  very  important 
bearing  upon  questions  of  disease.  When  disease 
occurs,  the  cells  of  the  body  offer  to  us  two  kinds  of 
spectacles.  Sometimes  we  see  that  the  cells  causing 
the  diseased  condition  are  more  or  less  of  the  sort 
which  naturally  belong  in  the  body  ;  that  they  are 
present  where  they  do  not  belong,  or  they  are  present 
where  they  ought  to  be,  but  in  excessive  quantity. 
There  is  a  kind  of  tumor  which  we  call  a  bony 
tumor.  It  consists  of  bone  cells  such  as  are  natur- 
ally present  in  the  body,  but  that  which  makes  this 
growth  of  bone  a  tumor  is  its  abnormal  dimensions, 
or  perhaps  its  being  altogether  in  the  wrong  place. 
The  second  sort  of  pathological  alteration,  which  I 
had  in  mind,  is  that  in  which  the  cells  really  change 
their  character.  Now,  the  young  cells  are  those  which 
can  change  most ;  in  which  the  genetic  restriction  has 
least  come  into  play  ;  and  accordingly  we  find  that  a 
large  number  of  dangerous,  morbid  growths,  tumors, 
arise  from  cells  of  the  young  type,  and  these  cells, 
having  an  extreme  power  of  multiplication,  grow 
rapidly,  and  they  may  assume  a  special  character  of 


THE  FOUR  LAWS  OF  AGE  225 

their  own  ;  their  genetic  restriction  has  not  gone  so 
far  that  all  their  possibilities  of  change  in  the  way  of 
differentiation  have  been  fixed ;  there  is  a  certain 
range  of  possibilities  still  open  to  them,  and  they  may 
turn  in  one  direction  or  the  other.  Hence  there  may 
be  pathological  growths  of  a  character  not  normally 
present  in  the  body.  It  seems  to  me,  so  far  as  my 
knowledge  of  this  subject  enables  me  to  judge,  to  be 
true  that  all  such  pathological  growths  depend  upon 
the  presence  of  comparatively  young  and  undifferen- 
tiated cells  beinor  turned  into  a  new  direction.  The 
problem  of  normal  development  and  of  abnormal 
structure  is  one  and  the  same.  Both  the  embryo- 
logist  and  the  anatomist,  on  the  one  hand,  and  the 
pathologist  and  the  clinician  on  the  other,  deal  ever 
with  these  questions  of  differentiation,  and  practically 
with  no  others.  All  that  occurs  in  the  body  is  the 
result  of  various  differentiations,  and  whether  we  call 
the  state  of  that  body  normal  or  pathological  matters 
little ;  still  the  cause  of  it  is  the  differentiation  of  the 
parts. 

The  second  of  the  collateral  topics  which  I  should 
like  briefly  to  allude  to  is  another  branch  of  the  study 
of  senescence.  The  fact  was  first  emphasised  by  the 
late  Professor  Alpheus  Hyatt  that  in  many  animals 
there  exist  parts  formed  in  an  early  stage  and  there- 
after never  lost.  The  chambered  nautilus  is  an  animal 
of  this  kind.  The  innermost  chamber  represents  the 
youngest  shell  of  the  nautilus,  and  as  its  age  increases, 
it  forms  a  new  chamber  in  its  shell,  and  so  yet  more 
15 


226  AGE,  GROWTH,  AND  DEATH 

and  more  until  the  coil  Is  complete.  When  we  examine 
a  shell  of  that  kind  we  see  permanently  before  us  the 
various  stages,  both  young  and  old,  as  recorded  in 
shell  formation.  And  so  too  in  the  sea-urchin,  and 
in  many  of  the  common  shell-fish,  we  find  the  double 
record,  of  youth  and  old  age,  preserved  permanently. 
This  has  made  it  possible  for  Professor  Hyatt  and 
for  Professor  Robert  T.  Jackson,  who  has  adopted  a 
similar  guiding  principle,  to  bring  new  light  into  the 
study  of  animal  changes,  and  to  attack  the  solution  of 
problems  which  without  the  aid  of  this  senescent  in- 
terpretation, if  I  may  so  term  it,  would  be  utterly 
impossible.  This  is  an  enticing  subject,  and  I  wish  I 
had  both  time  and  competency  to  dwell  upon  it.  But 
it  is  aside,  as  you  see,  from  the  main  inquiries  with 
which  we  have  been  occupied,  for  our  inquiries  con- 
cern chiefly  the  effect  of  cell-change  upon  the  proper- 
ties of  the  body,  and  the  correlation  of  cell-change 
with  aofe. 

A  natural  branch  of  our  topic  is,  however,  that  of 
longevity,  the  duration  of  life,^  Concerning  this,  we 
have  very  little  that  is  scientifically  satisfactory  that 
we  can  present.  We  know,  of  course,  as  a  funda- 
mental principle,  that  every  animal  must  live  long 
enough  to  reproduce  its  kind.  Did  that  not  occur, 
the  species  would  of  course  become  extinct,  and  the 
mere  fact  that  the  species  is  existing  proves,  of  course, 

*  We  are  indebted  to  August  Weissmann  for  raising  the  discussion  of  longevity 
to  the  level  of  science.  His  essay,  Ueber  die  Dattcr  des  Lebcus  (Jena,  1S82),  is 
by  far  the  best  on  the  subject  known  to  me,  and  includes  numerous  data  on  the 
longevity  of  animals. 


THE  FOUR  LAWS  OF  AGE  227 

this  simple  fact — that  life  has  lasted  long  enough  for 
the  parents  to  produce  offspring.  The  consideration 
of  this  fact  has  led  certain  naturalists  to  the  supposi- 
tion that  reproduction  is  the  cause  of  the  termination 
of  life  ;  but  it  is  not,  it  seems  to  me,  at  all  to  be  so 
interpreted.  We  know,  in  a  general  way,  that  large 
animals  live  longer  than  small  ones.  The  elephant  is 
longer  lived  than  the  horse,  the  horse  than  the  mouse, 
the  whale  than  the  fish,^  the  fish  than  the  insect,  and 
so  on  throuofh  innumerable  other  instances.  At  first 
this  seems  a  promising  clue,  but  if  we  think  a  moment 
longer  we  recognise  quickly  the  fact  that  a  parrot, 
which  is  much  smaller  than  a  dog,  may  live  one 
hundred  years,  whereas  a  dog  is  very  old  at  twenty. 
There  are  insects  which  live  for  many  years,  like  the 
seventeen-year  locusts,  and  others  which  live  but  a 
single  year  or  a  fraction  even  of  one  year,  and  yet  the 
long-lived  and  the  short-lived  may  be  of  the  same 
size.  It  is  evident,  therefore,  that  size  is  not  in  itself 
properly  a  measure  of  the  length  of  life.2  Another 
supposition,  which  at  first  sounds  very  attractive,  is 
that  which  explains  the  duration  of  life  by  the  rate  of 
wear,  of  the  using  up,  of  the  wearing  out,  of  the 
body.  This  theory  has  been  particularly  put  forward 
by  Professor  Weissmann,  who  in  his  writings  calls  it 
the  Abmitzungstheorie — the  theory  of  the  wearing  out 
of  the  body.      But  the  body  does  not  really  wear  out 

»  But  there  are  some  species  of  fish  which  outlive  whales  ;  thus  the  European 
carp  is  said  to  live  more  than  a  century. 

^  See  Appendix  No.  IV,  F.  A.  Lucas's  letter. 


228  AGE,  GROWTH,  AND  DEATH 

in  that  sense.  It  goes  on  performing  the  functions 
for  a  long  time,  and  after  each  function  is  performed 
the  body  is  restored,  and  we  do  not  find  at  death  that 
the  parts  have  worn  out.  But,  as  we  have  seen,  we 
do  find  at  death  that  there  has  been  an  extensive 
cytomorphosis,  cell-change,  and  that  the  living  ma- 
terial, after  having  acquired  its  differentiation,  passes 
now  in  one  part,  now  in  another,  then  in  a  third,  to  a 
yet  further  stage,  that  of  degeneration,  and  the  result 
of  degeneration,  or  atrophy,  as  the  case  may  be,  is 
that  the  living  protoplasm  loses  its  living  quality  and 
becomes  dead  material,  and  necessarily  the  functional 
activity  ceases.  We  must,  it  seems  to  me,  conclude 
that  longevity,  the  duration  of  life,  depends  upon  the 
rate  of  cytomorphosis.  If  that  cytomorphosis  is  rapid, 
the  fatal  condition  is  reached  soon,  if  it  is  slow,  the 
fatal  condition  is  postponed.  And  cytomorphosis  in 
various  species  and  kinds  of  animals  must  proceed 
at  different  rates  and  at  different  speeds  at  different 
ages.  Birds  grow  up  rapidly  during  their  period  of 
development ;  the  cell-change  occurs  at  a  high  speed, 
far  higher  than  that  which  occurs  in  man,  probably, 
during  his  period  of  development.  But  after  the  bird 
has  acquired  its  mature  development,  it  goes  on  almost 
upon  a  level  for  a  long  time  ;  the  bird  which  becomes 
mature  in  a  single  year  may  live  for  a  hundred  or 
even  more.  There  can  be  during  these  hundred  years 
but  a  very  slow  rate  of  change.  But  in  a  mammal,  a 
dog  or  a  cat,  creatures  of  about  the  same  bulk  as 
some  large  birds,  we  find  that  the  early  development  is 


THE  FOUR  LAWS  OF  AGE  229 

at  a  slower  rate.  The  mammals  take  a  much  longer 
period  to  pass  through  their  infancy  and  reach  their 
maturity,  but  after  they  have  reached  their  maturity 
they  do  not  sustain  themselves  so  long.  Their  later 
cytomorphosis  occurs  at  a  higher  speed  than  the  bird's. 
This  is  a  field  of  study  which  we  can  only  recognise 
the  existence  of  at  present,  and  which  needs  to  be 
explored  before,  to  any  general,  or  even  to  a  special 
scientific,  audience,  any  promising  hypotheses  can  be 
presented.  Definite  conclusions  are  of  course  still 
more  remote. 

Next  as  regards  death.  The  body  begins  its  de- 
velopment from  a  single  cell,  the  number  of  cells 
rapidly  increases,  and  they  go  on  and  on  increasing 
through  many  years.  Their  whole  succession  we  may 
appropriately  call  a  cycle.  Each  of  our  bodies  repre- 
sents a  cell  cycle.  When  we  die,  the  cycle  of  cells 
gives  out,  and,  as  I  have  explained  to  you  in  a  pre- 
vious lecture,  the  death  which  occurs  at  the  end  of 
the  natural  period  of  life  is  the  death  which  comes 
from  the  breakingr  down  of  some  essential  thingr — 
some  essential  group  of  members  of  this  cell  cycle  ; 
and  then  the  cycle  itself  collapses.  But  the  death  is 
the  result  of  changes  which  have  been  going  on 
through  the  successive  generations  of  cells  making 
up  this  cycle.  There  are  unicellular  organisms;  these 
also  die  ;  many  of  them,  so  far  as  we  can  now  deter- 
mine, never  have  any  natural  death,  but  there  are 
probably  others  in  which  natural  death  may  occur.  It 
is  evident  that  the  death  of  a  unicellular  organism  is 


230  AGE,  GROWTH,  AND  DEATH 

comparable  to  the  death  of  one  cell  in  our  own  bodies. 
It  is  not  properly  comparable  to  the  death  of  the 
whole  body,  to  the  ending-up  of  the  cell  cycle.  August 
Weissmann  was  led  to  a  series  of  erroneous  notions 
concerning  death  by  his  failure  to  distinguish  between 
the  death  of  a  cell  and  the  death  of  a  cycle  of  cells. 
Let  him  serve  as  a  warning  to  us.  Is  there  anything 
like  a  cell  cycle  among  the  lower  organisms  ?  among 
the  protozoa,  as  the  lowest  animals  are  called  ?  It 
has  been  maintained  by  a  French  investigator,  by  the 
name  of  Maupas,  that  such  a  cycle  does  exist,  that 
even  in  these  low  organisms  there  is  a  cell  which 
begins  the  development,  and  that  gradually  the  loss 
in  the  power  of  cell  multiplication  goes  on  until  the 
cycle  gives  out  and  has  to  be  renewed  by  a  rejuvenes- 
cent process,  and  this  rejuvenating  process  he  thinks 
he  has  found  in  the  so-called  conjugating  act  of  these 
animals,  in  which  there  occurs  a  curious  migration  of 
the  nucleus  of  one  individual  into  the  cell  body  of 
another.  Whether  he  is  right  or  not  remains  still  to 
be  determined.  It  means  much  that  Professor  G.  N. 
Calkins,  one  of  the  world  authorities  on  protozoa  and 
easily  the  foremost  American  master  of  this  branch 
of  zoology,  thinks  that  cyclical  development  rules  the 
protozoa,  each  cycle  ending  with  natural  death.  You 
will  recognise,  I  hope,  from  what  I  have  said,  that  we 
have  now  some  kind  of  measure  of  what  constitutes 
old  and  young.  We  can  observe  the  difference  in  the 
proportion  of  protoplasm  and  nucleus,  the  increase  or 
diminution,  as  the  case  may  be,  of  one  or  the  other. 


THE  FOUR  LAWS  OF  AGE  231 

If  it  be  true  that  there  is  among  protozoa,  among 
unicellular  animals,  anything  comparable  to  the 
gradual  decline  in  the  growth  power  which  occurs 
in  us,  we  shall  expect  it  to  be  revealed  in  the  con- 
dition of  the  cells — to  see  in  those  cells  which  are  old 
an  increase  in  the  proportion  and  in  the  differentiation 
of  their  protoplasm,  and  consequently  a  diminution  in 
the  relative  amount  of  nucleus.  That  subject  is  now 
being  investigated,  and  we  shall  probably  know,  within 
a  few  years  at  least,  something  positive  in  this  direc- 
tion. At  present  we  are  reduced  to  posing  our 
question.      We  must  wait  patiently  for  the  answer. 

The  scientific  man  has  many  occasions  for  patience. 
He  has  to  make  his  investigations  rather  where  he 
can  than  where  he  would  like  to.  Certain  thing-s  are 
accessible  to  our  instruments  and  methods  of  research 
at  the  present  time,  but  other  things  are  entirely 
hidden  from  us  and  inaccessible  at  the  present.  We 
are  indeed,  more  perhaps  than  people  in  any  other 
profession  of  life,  the  slaves  of  opportunity.  We 
must  do  what  we  can  in  the  way  of  research,  not 
always  that  which  we  should  like  most  to  do.  Per- 
haps a  time  will  come  when  many  of  the  questions 
connected  with  the  problems  of  growing  old,  which 
we  can  now  put,  will  be  answered,  because  oppor- 
tunities which  we  have  not  now  will  exist  then. 
Scientific  research  offers  to  its  devotees  some  of  the 
purest  delights  which  life  can  bring.  The  investigator 
is  a  creator.  Where  there  was  nothing-  he  brines 
forth  something.     Out  of  the  void  and  the  dark,  he 


232  AGE,  GROWTH,  AND  DEATH 

creates  knowledge,  and  the  knowledge  which  he  gath- 
ers is  not  a  precious  thing  for  himself  alone,  but 
rather  a  treasure  which  by  being  shared  grows  ;  if  it 
is  given  away  it  loses  nothing  of  its  value  to  the  first 
discoverer,  but  acquires  a  different  value  and  a  greater 
usefulness  that  it  adds  to  the  total  resources  of  the 
world.  The  time  will  come,  I  hope,  when  it  will  be 
generally  understood  that  the  investigators  and  think- 
ers of  the  world  are  those  upon  whom  the  world 
chiefly  depends.  I  should  like,  indeed,  to  live  to  a 
time  when  it  will  be  universally  recognised  that  the 
military  man  and  the  government-maker  are  types 
which  have  survived  from  a  previous  condition  of 
civilisation,  not  ours  ;  and  when  they  will  no  longer 
be  looked  upon  as  the  heroes  of  mankind.  In  that 
future  time  those  persons  who  have  really  created 
our  civilisation  will  receive  the  acknowledgment  which 
is  their  due.  Let  these  thoughts  dwell  long  in  your 
meditation,  because  it  is  a  serious  problem  in  all  our 
civilisation  to-day  how  to  secure  due  appreciation  of 
the  value  of  thought  and  how  to  encourage  it.  I 
believe  every  word  spoken  in  support  of  that  great 
recognition  which  is  due  to  the  power  of  thought  is 
a  good  word  and  will  help  forward  toward  good 
results. 

In  all  that  I  have  said,  you  will  recognise  that  I 
have  spoken  constantly  of  the  condition  of  the  living 
material.  If  it  is  in  the  young  state  it  has  one  set  of 
capacities.  If  it  is  differentiated,  it  has,  according  to 
the  nature  of  its  differentiation,  other  kinds  of  capa- 


THE  FOUR  LAWS  OF  AGE  233 

cities.  We  can  follow  the  changing  structure  with 
the  microscope.  We  can  gain  some  knowledge  of  it 
by  our  present  chemical  methods.  Fragmentary  as 
that  knowledge  is,  nevertheless,  it  sufifices  to  show  to  us 
that  the  condition  of  the  living  niate7''ial  is  essential  and 
determines  what  the  living  inaterial  can  do.  I  should 
like  to  insist  for  a  moment  upon  this  conception,  be- 
cause it  is  directly  contrary  to  a  conception  of  living 
material  which  has  been  widely  prevalent  in  recent 
years,  much  defended  and  popularly  presented  on 
many  different  occasions.  The  other  theory,  the  one 
to  which  I  cannot  subscribe,  may  perhaps  be  most 
conveniently  designated  by  the  term — the  theory  of 
life  units.  It  is  held  by  the  defenders  of  this  faith 
that  the  living  substance  contains  particles,  very  small 
in  size,  to  which  the  vital  properties  are  especially 
attached.  They  look  at  a  cell  and  find  that  it  has 
water,  or  water  containing  a  small  amount  of  salts  in 
solution,  filling  up  spaces  between  the  threads  of  pro- 
toplasm. Water  is  not  alive.  They  see  in  the  proto- 
plasm granules  of  one  sort  and  another,  in  plants 
chlorophyll,  in  animals  perhaps  fat  or  some  other 
material.  That  is  not  living  substance,  and  so  they 
go,  striking  out  from  their  conception  of  the  living 
material  in  the  cell  one  after  another  of  these  com- 
ponent parts  until  they  get  down  to  something  very 
small,  which  they  regard  as  the  life  unit.  I  do  not 
believe  these  life  units  exist.  It  seems  to  me  that  all 
these  dead  parts,  as  this  theory  terms  them,  are  parts 
of  the  living  cell.     They  are  factors  which  enable  the 


234  AGE,  GROWTH,  AND  DEATH 

functions  of  life  to  go  on.  Other  conditions  are  also 
there,  and  to  no  one  of  them  does  the  quality  of  life 
properly  attach  itself.  Of  life  units  there  is  an  ap- 
palling array.  The  most  estimable  of  them,  in  my 
opinion,  are  the  life  units  which  were  hypothetically 
created  by  Charles  Darwin  in  his  theory  of  pangenesis. 
He  assumed  that  there  were  small  particles  (gem- 
mules)  thrown  off  from  different  portions  of  the  body 
circulating  throughout  the  body,  gathering  sometimes 
in  the  germ  cells.  These  particles  he  assumed  to  take 
up  the  qualities  of  the  different  parts  of  the  body 
from  which  they  emanated,  and  by  gathering  together 
in  immense  numbers  in  the  germ  cells  to  accomplish 
the  hereditary  transmission.  We  know  now  that  this 
theory  is  not  necessary,  that  it  is  not  the  correct 
theory.  But  at  the  time  that  Darwin  promulgated  it, 
it  was  a  perfectly  sound,  defensible  theory,  a  theory 
which  no  one  considering  fairly  the  history  of  bio- 
logical knowledge  ought  to  criticise  unfavourably.  It 
was  a  fine  mental  achievement,  but  I  should  like  also 
to  add  that  of  all  the  many  theories  of  life  units,  this 
of  Darwin  is  the  only  one  which  seems  to  me  intel- 
lectually entirely  respectable.  Of  supposed  structural 
life  units  there  is  a  great  variety.  Besides  the  gem- 
mules  of  Darwin,  there  were  the  physiological  units 
of  Herbert  Spencer.  Professor  Haeckel,  the  famous 
German  writer,  has  structural  life  units  of  his  own 
which  he  terms  plastidules ;  he  gave  his  theory  the 
charming  alliterative  title  of  perigenesis  of  the  plasti- 
dules ;  the  rhythm  of  it  must  appeal  to  you  all,  though 


THE  FOUR  LAWS  OF  AGE  235 

i 

the  hypothesis  had  better  be  forgotten.  Then  came 
NageH,  the  great  botanist,  who  spoke  of  the  Idio- 
plasma-Theilchen.  Then  Weisner,  also  a  botanist, 
who  spoke  of  the  plassomes.  Our  own  Professor 
Whitman  attributed  to  his  life  units  certain  other  es- 
sential qualities  and  called  them  idiosomes.  A  German 
zoologist,  Haacke,  has  called  them  gemmules.  An- 
other German  writer,  a  Leipzig  anatomist,  Altmann, 
calls  them  granuli.  Now  these  different  life  units,  of 
which  I  have  read  you  briefly  the  names,  are  not 
identical  according  to  these  authors.  Everybody  else's 
life  units  are  wrong,  falsely  conceived,  and  endued 
with  qualities  which  they  do  not  combine.  Here  is 
a  curious  assemblage  of  "  doxies,"  and  each  writer 
is  orthodox  and  all  the  others  are  heterodox  ;  and  I 
find  myself  viewing  them  all  from  the  standpoint  of 
my  "doxy,"  that  of  the  structural  quality  of  the  living 
matter,  and,  therefore,  interpreting  every  one  of  these 
conceptions  as  heterodox,  not  sound  doctrine,  but 
something  to  be  rejected,  condemned,  and  fought 
against.  These  theories  of  life  units  have  filled  up 
many  books.  Among  the  most  ardent  defenders  of 
the  faith  in  life  units  is  Professor  Weismann,  whose 
theories  of  heredity  many  of  you  have  heard  discussed ; 
though  I  doubt  if  many  of  you,  unless  you  recall  what 
I  said  previously,  are  aware  of  the  fact  that  the  es- 
sential part  of  Weismann's  doctrine  was  the  adoption 
of  the  theory  of  germinal  continuity  originated  by 
Professor  Nussbaum,  whose  name  by  a  strange  in- 
justice has  been  too  seldom  heard  in  these  discussions* 


236  AGE,  GROWTH,  AND  DEATH 

Weismann  has  gone  much  farther  in  the  elaboration 
of  the  conception  of  hfe  units  than  any  of  the  other 
writers.  He  thinks  the  smallest  of  the  life  units  are 
biophores.  A  group  of  biophores  brought  together 
constitutes  another  order  of  life  units  which  he  calls 
determinants;  the  determinants  are  again  grouped  and 
form  ids ;  and  the  ids  are  again  grouped  and  form 
idants.  If  you  want  to  accept  any  theory  of  life  units, 
I  advise  you  to  accept  that  of  Weismann,  for  it  offers 
a  large  range  for  the  imagination,  and  has  a  much 
more  formidable  number  of  terms  than  any  other, 

I  want  to  pass  now  to  an  utterly  different  line  of 
study,  the  question  of  psychological  development.  If 
it  be  true  that  the  development  is  most  rapid  at  first, 
slower  later,  we  should  expect  to  find  proof  of  that 
rate  in  the  progress  of  mental  development.  In  other 
words,  we  should  expect  to  find  that  the  baby  de- 
veloped faster  than  the  child  mentally,  that  the  child 
developed  faster  than  the  young  man,  and  the  young 
man  faster  than  the  old.  And  do  you  not  all  instinc- 
tively feel  immediately  that  the  general  assertion  is 
true?  In  order,  however,  that  you  may  more  fully 
appreciate  what  I  believe  to  be  the  fact  of  mental 
development  going  on  with  diminishing  rapidity,  I 
should  like  to  picture  to  you  briefly  some  of  the 
things  which  the  child  achieves  during  the  first  year 
of  its  life.^      When  the  child  is  born,  it  is  undoubtedly 

1  I  am  indebted  to  Dr.  Benjamin  Rand  of  Harvard  University  for  guidance 
to  the  literature  upon  the  subject  of  the  mental  development  of  children.  The 
account  in  the  text  is  the  result  of  reworking  the  recorded  data,  so  as  to 
elucidate  the  relation  of  the  child's  mental  progress  to  its  age,   none  of    the 


THE  FOUR  LAWS  OF  AGE  237 

supplied  with  a  series  of  the  indispensable  physiologi- 
cal functions,  all  those  which  are  concerned  with  the 
taking  in  and  utilising  of  food.  The  organs  of  diges- 
tion, assimilation,  circulation,  and  excretion  are  all 
functionally  active  at  birth.  The  sense  organs  are  also 
able  to  work.  Sense  of  taste  and  of  smell  are  doubt- 
fully present.  It  is  maintained  that  they  are  already 
active,  but  they  do  not  show  themselves  except  in  re- 
sponse to  very  strong  stimulation.  Almost  the  only 
additional  faculty  which  the  child  has  is  that  of  mo- 
tion, but  the  motions  of  the  new-born  baby  are  per- 
fectly irregular,  accidental,  purposeless,  except  the 
motions  which  are  connected  with  the  function  of 
sucking,  upon  which  the  child  depends  for  its  nourish- 
ment. The  instinct  of  sucking,  the  baby  does  have  at 
birth.  It  might  be  described  as  almost  the  only 
equipment  beyond  the  mere  physiological  working  of 
its  various  organs.  But  at  one  month  we  find  that 
this  uninformed  baby  has  made  a  series  of  important 

authorities  I  have  consulted  having  presented  the  matter  with  special  reference 
to  the  age  rate.    I  have  drawn  chiefly  from  the  following  publications  : 

Compayre  "La  psychologie  de  Yeniant," Revttepkilosophique,  vi.,  1878,  464- 
481. 

Ch.  Darwin,  "Biographical  Sketch  of  an  Infant,"  Mind,  ii.,  1877,  285-294. 

Louise  Hogan,  Study  of  a  Child,  New  York,  1898. 

Kussmaul,  Seeletileben  des  neugeborenen  Menschen,  i8g6. 

Kathleen  Moore,  "Mental  Development  of  a  Child,"  Psychol  Review,  Sup- 
plement, Oct.,  1896. 

Oppenheim,  The  Development  of  a  Child,  New  York,  1898. 

Wm.  Preyer,  The  Mind  of  the  Child.  Translated  by  H.  W.  Brown.  2  vols. 
One  of  the  most  important  and  suggestive  works  on  the  subject. 

M.  W.  Shinn,  The  Biography  of  a  Baby,  Boston,  1900.  An  excellent  book, 
both  authoritative  and  readable. 

Amy  E.  Tanner,  The  Child,  New  York,  1904. 


238  AGE,  GROWTH,  AND  DEATH 

discoveries.  It  has  learned  that  there  are  sensations, 
that  they  are  interesting ;  it  will  attend  to  them.  You 
all  know  how  a  baby  of  one  month  will  stare  ;  the 
eyes  will  be  fastened  upon  some  brig-ht  and  interest- 
ing object.  At  the  end  of  a  month  the  baby  shows 
evidences  of  having  ideas  and  bringing  them  into 
correlation, — association,  as  one  more  correctly  ex- 
presses it, — because  already  after  one  month,  when  held 
in  the  proper  position  in  the  arms,  it  shows  that  it 
expects  to  be  fed.  There  is,  then,  already  evidence 
and  trace  of  memory.  At  two  months  much  more 
has  been  achieved.  The  baby  evidently  learns  to 
expect  things.  It  expects  to  be  fed  at  certain  times  ; 
it  has  made  the  great  discovery  of  the  existence  of 
time.  And  it  has  made  the  discovery  of  the  existence 
of  space,  for  it  will  follow  to  some  extent  the  bright 
light ;  it  will  hold  its  head  in  a  certain  position  to 
catch  a  sound  apparently  from  one  side ;  or  to  see  in 
a  certain  direction.  The  sense  of  space  and  time  in 
the  baby's  mind  is,  of  course,  very  imperfect,  doubt- 
less, at  this  time,  but  those  two  non-stuff  realities 
about  which  the  metaphysicians  discuss  so  much,  the 
two  realities  of  existence  which  are  not  material,  the 
baby  at  this  time  has  discovered.  Perhaps,  had  some 
great  and  wonderfully  endowed  person  existed  who 
preserved  the  memory  of  his  own  psychological  his- 
tory, of  his  development  during  babyhood,  we  should 
have  been  spared  the  gigantic  efforts  of  the  meta- 
physicians to  explain  how  the  notions  of  space  and 
time  arose.     Without  knowing  how,  the  baby  has  ac- 


THE  FOUR  LAWS  OF  AGE  239 

quired  them,  and  has  already  become  a  rudimentary 
metaphysician.  We  see,  also,  at  the  end  of  the  third 
month,  that  the  baby  has  made  another  remarkable 
discovery.  It  has  found  not  merely  that  its  muscles 
will  contract  and  jerk  and  throw  its  parts  about,  which 
surely  was  earlier  a  great  delight  to  it;  but  that 
the  muscles  can  contract  in  such  a  way  that  the  move- 
ment will  be  directed  ;  there  is  a  co-ordination  of  the 
muscular  movements.  I  should  like  to  read  to  you 
just  these  three  or  four  lines  from  Miss  Shinn,  who 
has  given  perhaps  the  best  story  of  the  development 
of  a  baby  which  has  yet  been  written.  This  is  not 
merely  my  opinion,  but  also  the  opinion  of  my  psycho- 
logical colleagues  at  Cambridge  whom  I  consulted 
before  venturing  to  express  the  idea  before  you,  and 
I  find  that  they  take  the  view  that  Miss  Shinn's  book, 
which  is  charmingly  written,  is  really  done  with  such 
precision  and  understanding  of  the  psychological  pro- 
blems involved  that  it  may  fairly  be  called  the  best  of 
the  books  treating  of  the  mental  development  of  a 
baby.  Miss  Shinn  says,  referring  to  the  condition  of 
the  child  at  the  end  of  two  months — "Such  is  the  mere 
life  of  vegetation  the  baby  lived  during  the  first  two 
months ;  no  grown  person  ever  experienced  such  an 
expansion  of  life  —  such  a  progress  from  power  to 
power  in  that  length  of  time."  She  is  not  thinking 
of  senescence,  as  we  have  been  thinking  of  it,  but  she 
makes  precisely  the  assertion,  which  seems  to  me  to 
be  true,  that  the  baby  in  two  months  has  accomplished 
an  amount  of  development  which  no  adult  is  capable 


240  AGE,  GROWTH,  AND  DEATH 

of.  And  now  at  three  months  we  find  another  great 
discovery  is  made  by  the  baby,  that  it  is  possible  to 
bring-  the  sensations  which  it  receives  into  combina- 
tion  with  the  movements  which  it  makes.  It  learns 
to  co-ordinate  its  sensory  impressions  and  its  motor 
responses.  We  hardly  realise  what  a  great  role  this 
adjustment,  between  what  our  muscles  can  do  and 
what  our  senses  tell  us,  plays  in  our  daily  life.  It  is 
the  fundamental  thing  in  all  our  daily  actions,  and 
though  by  habit  we  perform  it  almost  unconsciously, 
it  is  a  thing  most  difficult  to  learn.  Yet  the  baby  has 
acquired  the  art,  though  he  only  gradually  gets  to  be 
perfect  in  it.  Again  we  see,  at  the  end  of  the  fourth 
month,  that  the  baby  begins  to  show  some  idea  of  an- 
other great  principle — the  idea  that  it  can  do  some- 
thing. It  shows  evidence  of  having  purpose  in  what 
it  does.  Its  movements  are  no  longer  purely  acci- 
dental. At  four  months  we  find  yet  another  equally 
astonishinof  addition  to  the  achievements  of  this  mar- 
vellous  baby.  He  makes  the  amazing  discovery  that 
the  two  sides  of  an  object  are  not  separate  things,  but 
are  parts  of  the  same.  When  a  face,  for  instance, 
disappears  by  a  person's  turning  around,  that  face,  to 
a  baby  of  one  month,  probably  simply  vanishes,  ceases 
to  exist :  but  the  baby  at  four  months  realises  that 
the  face  and  the  back  of  the  head  belong  to  the  same 
object.  He  has  acquired  the  idea  of  objects  existing 
in  the  world  around  him.  That  is  an  enormous 
achievement,  for  this  little  baby  has  no  instructor;  he 
is  finding  out  these  things  by  his  own  unaided  efforts. 


THE  FOUR  LAWS  OF  AGE  241 

Then  at  five  months  begins  the  age  of  handhng  when 
the  baby  feels  of  everything.  It  feels  urgently  of  all 
the  objects  which  it  can  get  hold  of  and  perhaps  most 
of  all  of  its  own  body.  It  is  finding  that  it  can  touch  its 
various  own  parts  and  that  when  its  hands  and  parts 
of  Its  own  body  come  in  contact  it  has  the  double 
sensations,  and  learns  to  bring  them  together  and 
thereby  is  manufacturing  in  its  consciousness  the  con- 
ception of  the  ego,  personal,  individual  existence,  an- 
other great  metaphysical  notion.  Descartes  has  said, 
''Cogito,  ergo  sum' — "  I  think,  therefore  I  am."  The 
baby,  if  he  had  written  in  Descartes's  place,  would 
have  said,  "  I  feel,  therefore  I  am."  The  first  five 
months  constitute  the  first  period  of  the  baby's  de- 
velopment Its  powers  are  formed,  and  the  founda- 
tions of  knowledge  have  been  laid.  The  second 
period  is  a  period  of  amazing  research,  constant,  un- 
interrupted, untiring;  renewed  the  instant  the  baby 
wakes  up,  and  kept  up  until  sleep  again  overtakes  It. 
In  the  six  months'  baby  we  find  already  the  notion  of 
cause  and  effect.  You  see  he  Is  dealing  mostly  In 
metaphysical  things,  getting  the  fundamental  con- 
cepts. That  there  Is  such  an  idea  as  cause  and  effect 
in  the  baby's  mind  is  clearly  shown  by  the  progress  of 
its  adaptive  intelligence.  It  evidently  has  now  distinct 
purposes  of  its  own.  It  shows  clearly  at  this  age  also 
another  thing  which  plays  a  constant  and  Important 
r6le  in  our  daily  life.  It  has  the  consciousness  of  the 
possibilities  of  human  intercourse  ;  It  wants  human 
companionship.  And  with  that  the  baby's  equipment 
16 


242  AGE,  GROWTH,  AND  DEATH 

to  start  upon  life  is  pretty  well  established.  It  has 
discovered  the  material  universe  in  which  it  lives,  the 
succession  of  time,  the  nature  of  space,  cause  and 
effect,  its  own  existence,  its  ego  and  its  relationship 
with  other  individuals  of  its  own  species.  Do  we  get 
at  any  time  in  our  life  much  beyond  this  ?  Not  very 
much  ;  we  always  use  these  things,  which  we  learn  in 
the  first  six  months,  as  the  foundation  of  all  our 
thought.  By  eight  months,  baby  is  upon  the  full 
career  of  experiment  and  observation.  Everything 
with  which  the  baby  comes  in  contact  interests  him. 
He  looks  at  it,  he  seizes  hold  of  it,  tries  to  pull  it  to 
pieces,  studies  its  texture,  its  tensile  strength,  and 
every  other  quality  it  possesses.  Not  satisfied  with 
that,  he  will  turn  and  apply  his  tongue  to  it,  putting 
it  in  his  mouth  for  the  purpose  of  finding  out  if  it  has 
any  taste.  In  doing  this,  hour  after  hour,  with  un- 
ceasing zeal,  never  interrupted  diligence,  he  rapidly 
gets  acquainted  with  the  world  in  which  he  is  placed. 
At  the  same  time  he  is  making  further  experiments 
with  his  own  body.  He  begins  to  tumble  about ; 
perhaps  learns  that  it  is  possible  to  get  from  one  place 
to  another  by  rolling  or  creeping,  and  slowly  he  dis- 
covers the  possibility  of  locomotion,  which  you  know 
by  the  end  of  the  year  will  have  so  far  perfected  itself 
that  usually  at  twelve  months  the  baby  can  walk. 
During  this  period  of  from  five  months  to  twelve  the 
baby  is  engaged  upon  a  career  of  original  research, 
unaided  much  by  anybody  else,  getting  doubtless  a 
little  help  and,  of  course,  a  great  deal  of  protection, 


THE  FOUR  LAWS  OF  AGE  243 

but  really  working  chiefly  by  himself.  How  wonder- 
ful it  all  is  !  Is  any  one  of  us  capable  of  beginning  at 
the  moment  we  wake  to  carry  on  a  new  line  of  thought, 
a  new  series  of  studies,  and  to  keep  it  up  full  swing, 
with  unabated  pace,  all  day  long  till  we  drop  asleep  ? 
Every  baby  does  that  every  day. 

When  we  turn  to  the  child  who  goes  to  school,  be- 
hold how  much  that  child  has  lost.  It  has  difficulties 
with  learning  the  alphabet.  1 1  struggles  slowly  through 
the  Latin  grammar,  painfully  with  the  subject  of 
geometry,  and  the  older  it  gets  the  more  difficult 
becomes  the  achievement  of  its  study.  The  power 
of  rapid  learning,  which  the  baby  has,  is  clearly 
already  lessened. 

The  introduction  of  athletics  affords  a  striking  illus- 
tration of  the  decline  of  the  learning  power  with  the 
progressing  years.  When  golf  first  came  in  it  was  con- 
sidered an  excellent  game  for  the  middle-aged;  and  you 
have  all  watched  the  middle-aged  man  play.  He  was 
so  awkward,  he  could  not  do  it.  Day  after  day  the 
man  of  forty,  fifty,  or  even  older,  would  go  to  the  golf 
field,  hoping  each  time  to  acquire  a  sure  stroke,  but 
never  really  acquiring  it.  The  young  man  learned 
better,  but  the  good  golf  players  are  those  who  begin 
as  children,  twelve  and  fourteen  years  of  age,  and  in 
a  few  months  become  as  expert  and  sure  as  their 
fathers  wished  to  become,  but  could  not.  In  bicycling 
it  was  the  same.  Eight  lessons  was  considered  the 
number  necessary  to  teach  the  intelligent  adult  to  ride 
a  wheel.    Three  for  a  child  of  eiorht.    And  an  indefinite 


244  AGE,  GROWTH,  AND  DEATH 

number  of  lessons,  ending  in  failure,  for  a  person  at 
seventy.  It  would  have  been  scientifically  interesting 
to  have  kept  an  exact  record  of  the  period  of  time 
which  it  took  at  each  age  to  learn  bicycling,  but  I 
think  enough  has  been  said  to  convince  you  that  if  we 
could  acquire  such  a  measure  of  psychological  develop- 
ment as  would  enable  us  to  express  its  rate  in  figures, 
we  should  be  able  to  construct  a  curve  like  the  curve 
which  I  showed  you  in  the  third  lecture  illustrating  the 
decline  in  the  rate  of  growth,  and  we  should  see  that 
during  the  early  years  of  life  the  decline  in  the  power 
of  learning  was  extremely  rapid,  during  childhood  less 
rapid,  during  old  age  very  slow.  But  the  great  part 
of  the  decline  would  occur  during  early  years. 

Here  we  see  the  principle  of  stability,  in  maturity, 
which  we  see  also  illustrated  in  structure  and  growth. 
The  mind  acquires  its  development;  it  retains  that  de- 
velopment in  the  adult  a  long  time.  But  surely  there 
comes  a  period  when  the  exercise  of  the  mind  is  dififi- 
cult.  It  requires  a  great  effort  to  do  something  new 
and  unaccustomed.  A  sense  of  fatigue  overwhelms 
us.  I  believe  that  this  principle  of  psychological  de- 
velopment, paralleling  the  career  of  physical  develop- 
ment, needs  to  be  more  considered  in  arranging  our 
educational  plans.  For  if  it  be  true  that  the  decline 
in  the  power  of  learning  is  most  rapid  at  first,  it  is 
evident  that  we  want  to  make  as  much  use  of  the  early 
years  as  possible — that  the  tendency,  for  instance, 
which  has  existed  in  many  of  our  universities,  to  post- 
pone the  period  of  entrance  into  college  Is  biologically 


THE  FOUR  LAWS  OF  AGE  245 

an  erroneous  tendency.  It  would  be  better  to  have  the 
young  man  get  to  college  earlier,  graduate  earlier,  get 
into  practical  life  or  into  the  professional  schools 
earlier,  while  the  power  of  learning  is  greater. 

Do  we  not  see,  in  fact,  that  the  new  ideas  are  indeed 
for  the  most  part  the  ideas  of  young  people  ?  As  Dr. 
Osier,  in  that  much-discussed  remark  of  his,  has  said, 
the  man  of  forty  years  is  seldom  the  productive  man. 
Dr.  Osier  also  mentioned  the  amiable  suororestion  of 
Trollope  in  regard  to  men  of  sixty,  which  has  been 
so  extremely  misrepresented  in  the  newspaper  discus- 
sions throughout  the  country,  causing  biologists  much 
amusement.  But  I  think  that  Dr.  Osier  probably  took 
a  far  too  amiable  view  of  mankind,  and  that  in  reality 
the  period  when  the  learning  power  Is  nearly  obliter- 
ated is  reached  in  most  individuals  very  much  earlier. 
Permit  me  to  read  to  you  a  quotation  from  a  lecture 
which  I  delivered  last  year  (1906)  before  the  Harvey 
Society: 

"  It  msiy  be  true  that  that  age  (40)  marks  in  intellectual  men 
usually  a  transition  or  the  point  where  the  accumulated  losses 
which  have  been  occurring  from  birth  on  reveal  their  effects  clearly, 
but  in  the  great  majority  of  men  comparative  mental  fixity  surely 
occurs  at  a  much  earlier  period.  If  you  will  allow  me  to  wander 
for  a  moment  from  the  strict  discussion  of  our  immediate  theme, 
I  should  like  to  refer  to  what  may  be  called  the  theory  of  perma- 
nent mental  fatigue.  The  organic  changes  which  go  on  in  the 
nervous  system  diminish  its  pliability  and  there  comes  a  time  when 
the  individual  finds  it  exceedingly  difficult  to  bring  his  mind  into 
any  unaccustomed  form  of  activity.  How  completely  we  are 
mastered  by  this  difficulty  is  often  hidden,  I   believe,  from  our 


246  AGE,  GROWTH,  AND  DEATH 

recognition  and  from  that  of  our  friends,  because  we  have  acquired 
certain  habits  of  activity  which  we  are  able  to  keep  up,  but  we 
are  not  able  without  ever-increasing  difficulty  to  turn  to  new 
forms  of  mental  activity,  or  in  other  words,  to  learn  new  things. 
When  we  grow  old  we  may  still  continue  to  do  well  the  kind  of 
thing  which  we  have  learned  to  do,  whether  it  be  paying  out  bills 
at  a  bank  or  paying  out  a  particular  set  of  scientific  ideas  to  a 
class  of  students.  If  we  try  to  overstep  the  limits  of  our  acquired 
expertness  we  find  that  we  are  held  up  by  this  sense  of  permanent 
mental  fatigue.  Usually  this  condition  comes  about  gradually, 
but  I  have  known,  as  I  presume  you  all  have,  several  cases  in 
which  it  has  appeared  suddenly,  where  a  man  who  up  to  a  certain 
time  was  fond  of  mental  exertion  suddenly  ceased  to  be  mentally 
active.  We  have  probable  illustrations  of  this  in  the  careers  of 
well-known  scientific  men.  I  think  the  theory  of  permanent 
mental  fatigue,  in  connection  with  the  theory  of  gradual  decline 
which  we  are  considering  this  evening,  could  be  usefully  devel- 
oped and  might  well  be  utilised  by  the  psychologists  in  their 
studies." 

As  in  every  study  of  biological  facts,  there  is  in  the 
study  of  senescent  mental  stability  the  principle  of  vari- 
ation to  be  kept  in  mind.  Men  are  not  alike.  The 
great  majority  of  men  lose  the  power  of  learning, 
doubtless  some  more  and  some  less,  we  will  say,  at 
twenty-five  years.  Few  men  after  twenty-five  are  able 
to  learn  much.  They  who  cannot,  become  day-labour- 
ers, mechanics,  clerks  of  a  mechanical  order.  Others 
probably  can  go  on  somewhat  longer,  and  obtain  higher 
positions;  and  there  are  men  who,  with  extreme  varia^ 
tions  in  endowment,  preserve  the  power  of  active  and 
original  thought  far  on  into  life.  These  of  course  are 
the  exceptional  men,  the  great  men. 


THE  FOUR  LAWS  OF  AGE  247 

We  have  lingered  so  long  together  studying  phe- 
nomena of  growth,  that  it  is  natural  to  allude  to  one 
more,  which  is  as  singular  as  it  is  interesting,  namely, 
the  increase  in  size  of  Americans.  It  was  first  demon- 
strated by  Dr.  Benjamin  A.  Gould  in  his  volume  of 
statistics  derived  from  the  records  of  the  Sanitary 
Commission — a  volume  which  still  remains  the  classic 
and  model  of  anthropometric  research.  Any  one,  how- 
ever, can  observe  that  the  younger  generation  of 
to-day  tends  conspicuously  to  surpass  its  parents  in 
stature  and  physical  development.  How  to  explain 
the  remarkable  improvement  we  do  not  know.  Our 
discovery  of  the  fact  that  the  very  earliest  growth  is  so 
enormously  rapid,  makes  that  earliest  period  especially 
important.  If  the  initial  growth  can  be  favoured,  a 
better  subsequent  development  presumably  would  re- 
sult. In  brief,  I  find  myself  led  to  the  hypothesis  that 
the  better  health  of  the  mothers  secures  improved 
nourishment  in  the  early  stages  of  the  offspring,  and 
that  the  maternal  vigour  is  at  least  one  important 
immediate  cause  of  the  physical  betterment  of  the 
children.  Much  is  said  about  the  degeneracy  of  the 
American  race,  but  the  contrary  is  true — the  Amer- 
ican race  surpasses  its  European  congeners  in  physical 
development. 

You  will  naturally  wish  to  ask,  before  I  close  the  series 
of  lectures,  two  questions.  One,  how  can  rejuvenation 
be  improved  ?  the  other,  how  can  senescence  be  de- 
layed ?  These  questions  will  strike  every  one  as  very 
practical.     But  the  first,  I  fear,  is  not  an  immediately 


248  AGE,  GROWTH,  AND  DEATH 

practical  question,  but  rather  of  scientific  interest,  for 
we  must  admit  that  the  production  of  young  individ- 
uals is,  on  the  whole,  very  well  accomplished  and  much 
to  our  satisfaction.  But  in  regard  to  growing  old,  in 
regard  to  senescence,  the  matter  is  very  different. 
There  we  should,  indeed,  like  to  have  some  principle 
given  to  us  which  would  retard  the  rate  of  senescence 
and  leave  us  for  a  longer  period  the  enjoyment  of  our 
mature  faculties.  I  can,  as  you  have  readily  surmised 
by  what  I  have  said  to  you,  present  to  you  no  new  rule 
by  which  this  can  be  accomplished,  but  I  can  venture 
to  suggest  to  you  that  in  the  future  deeper  insight 
into  these  mysteries  probably  awaits  us,  and  that  there 
may  indeed  come  a  time  when  we  can  somewhat  reg- 
ulate these  matters.  If  it  be  true  that  the  growing  old 
depends  upon  the  increase  of  the  protoplasm,  and  the 
proportional  diminution  of  the  nucleus,  we  can  perhaps 
in  the  future  find  some  means  by  which  the  activity  of 
the  nuclei  can  be  increased  and  the  younger  system 
of  organisation  thereby  prolonged.  That  is  only  a 
dream  of  the  possible  future.  It  would  not  be  safe 
even  to  call  it  a  prophecy.  But  stranger  things  and 
more  unexpected  have  happened,  and  perhaps  this  will 
also. 

I  do  not  wish  to  close  without  a  few  words  of  warn- 
ing explanation.  The  views  which  I  have  presented 
before  you  in  this  series  of  lectures  I  am  personally 
chiefly  responsible  for.  Science  consists  in  the  dis- 
coveries made  by  individuals,  afterwards  confirmed  and 
correlated  by  others,  so  that  they  lose  their  personal 


THE  FOUR  LAWS  OF  AGE  .049 

character.  You  ought  to  know  that  the  interpreta- 
tions which  I  have  offered  you  are  still  largely  in  the 
personal  stage.  Whether  my  colleagues  will  think  that 
the  body  of  conceptions  which  I  have  presented  are 
fully  justified  or  not,  I  cannot  venture  to  say.  I  have 
to  thank  you  much,  because  between  the  lecturer  and 
his  audience  there  is  established  a  personal  relation, 
and  I  feel  very  much  the  compliment  of  your  presence 
throughout  this  series  of  lectures,  and  of  the  very 
courteous  attention  which  you  have  given  me. 

To  recapitulate — for  we  have  now  arrived  at  the  end 
of  our  hour — it  must  be  said  first  that  all  of  the  conclus- 
ions presented  are  based  upon  the  laws  of  cytomor- 
phosis,  in  other  words,  of  the  change  in  structure  which 
occurs  not  only  in  a  single  cell,  but  progressively  in 
successive  generations  of  cells.  We  can  formulate  the 
following  laws  of  cytomorphosis: 

Fii^st,  cytomorphosis  begins  with  an  undifferenti- 
ated cell. 

Second,  cytomorphosis  is  always  in  one  direction, 
through  progressive  differentiation  and  degeneration 
towards  the  death  of  the  cells. 

Third,  cytomorphosis  A^aries  in  degree  characteris- 
tically for  each  tissue  (hence  in  the  adult  higher  ani- 
mals nearly  all  stages  of  cytomorphosis  may  co-exist). 

We  may  add  that  reversed  cytomorphosis  is  not 
known  to  occur,  or,  in  other  words,  differentiated  ma- 
terial cannot  be  restored  to  the  undifferentiated  con- 
dition. 

Finally,  if  my  arguments  before  be  correct,  we  rnay 


2  50  AGE,  GROWTH,  AND  DEATH 

say  that  we  have  estabHshed  the  following  four  laws 
of  age  : 

First,  rejuvenation  depends  on  the  increase  of  the 
nuclei. 

Second,  senescence  depends  on  the  increase  of  the 
protoplasm,  and  on  the  differentiation  of  the  cells. 

Third,  the  rate  of  growth  depends  on  the  degree  of 
senescence. 

Fourth,  senescence  is  at  its  maximum  in  the  very- 
young  stages,  and  the  rate  of  senescence  diminishes 
with  age. 

As  the  corollary  from  these,  we  have  this — natural 
death  is  the  consequence  of  cellular  differentiation. 


APPENDICES 


251 


APPENDIX   I.     GROWTH  OF  RABBITS. 

'T'HE  data  which  I  have  collected  concerning  the  growth  of 
^  rabbits  have  not  been  published  hitherto,  and  are  therefore 
printed  here.  It  is  from  the  average  of  the  percentage  incre- 
ments that  Figures  35  and  36  were  constructed. 

There  are  certain  precautions  in  making  weighings,  not  only  of 
rabbits  but  also  of  other  animals,  which  were  found  necessary. 
As  soon  as  a  litter  was  born  and  the  amniotic  fluid  dried  off  from 
the  fur  of  the  young,  each  individual  was  weighed,  the  sex  noted, 
and  an  exact  description  of  all  the  markings,  which  do  not  alter 
after  birth,  written  down.  The  litter  was  numbered,  and  the 
date  of  birth  and  the  parentage,  or  at  least  the  maternal  par- 
entage, recorded. 

To  identify  the  rabbits  they  were  marked  with  spots  of  nitrate 
of  stiver.  It  may  be  mentioned  in  passing  that  the  Guinea-pigs, 
of  which  there  was  a  large  number  raised,  can  usually  be  indi- 
vidually identified  by  their  natural  markings.  I  found  it  a 
great  convenience  to  give  mnemonic  names  to  all  the  pigs 
of  which  I.  followed  the  growth,  so  that  the  name  would  sug- 
gest the  appearance  of  the  individual  pig.  For  the  most  part 
the  names  referred  directly  to  the  marking,  for  instance,  "  Brown 
rump,"  "Saddle  back,"  "Snout,"  etc., — but  often  the  allusion 
was  more  remote,  as  for  instance,  "Hypocrite,"  whose  head, 
seen  from  one  side,  appeared  entirely  black,  from  the  other,  en- 
tirely white.  The  record  having  been  started,  the  next  thing 
was  to  enter  in  a  diary  all  the  dates  during  the  remainder  of 
the  year  upon  which  the  litter  in  question  was  to  be  weighed.' 
The  plan  adopted  after  a  little  experience  was  to  weigh  each  in- 
dividual every  day  up  to  40  days,  then  every  fifth  day  up  to  215 

'  The  apparatus  devised  for  calculating  the  required  dates  mechanically  is 
described  in  Appendix  VI. 

253 


254 


AGE,  GROWTH,  AND  DEATH 


days,  and  then  after  every  thirtieth  day,  and  to  avoid  accidental 
variations,  also  five  days  before  and  five  days  after  each  thirtieth 
day  :  for  instance,  the  months  being  assumed  at  30  days,  the  ani- 
mals would  be  weighed  for  the  eighth  month  at  240,  also  at  235 
and  245  days,  and  the  next  set  for  nine  months,  265,  270,  and  275, 
and  so  on  to  the  end  of  the  second  year  after  birth,  at  which  age 
the  observations  were  stopped.  Of  no  individual  have  I  an  abso- 
lutely complete  series  of  weights,  but  of  a  good  many  the  series 
are  nearly  complete.    A  very  few  of  my  animals  died  from  disease. 


GROWTH    OF    RABBITS.     A,   MALES 


Total 

Increase 

Average 

Daily 

Av.  Daily 

Age 
Days 

Weight 
Grams 

Obs. 

Average 

Over  Last 
Measurement 

Daily 
Increase 

Per  Cent. 
Increase 

Per  Cent. 
Increase 

0 

201.3 

4 

50.3 

I 

238.9 

4 

59-7 

9-4 

9.4 

18.5  1 

2 

272.6 

4 

68.1 

8.4 

8.4 

14. 1 

3 

344-9 

4 

86.2 

18. 1 

18. 1 

26.6  y 

17.6 

4 

402.3 

4 

100.6 

14-4 

14.4 

16.7 
12.3  J 

5 

452.2 

4 

113.0 

12.4 

12.4 

6 

287.0 

2 

143-5 

30.5 

30.5 

26.9^ 

7 

622.5 

4 

155-6 

12. 1 

12. 1 

8.4 

8 

708.1 

4 

177.0 

21.4 

21.4 

13.8   V 

13-5 

9 

786.6 

4 

196.6 

19.6 

19.6 

II. I 

10 

844.6 

4 

2X1. 1 

14.5 

14-5 

7-4J 

II 

922.0 

4 

230.5 

19.4 

19.4 

9.2 1 

12 

993-2 

4 

248.3 

17.8 

17-8 

7.7 

13 

683.0 

2 

341-5 

93-2 

93-2 

37-5  } 

15.6 

14 

1121.2 

4 

280.3 

—61.2 

— 61.2 

—17.9 
41.6  J 

15 

794.0 

2 

397.0 

116. 7 

116. 7 

16 

1265.0 

4 

316.2 

—80.8 

—80.8 

— 20. 4  ^ 

17 

1356.0 

4 

339.0 

22.8 

22.8 

7.2 

18 

922.0 

2 

461.0 

122.0 

122.0 

36.0  V 

10.  T 

19 

1479-5 

4 

369-9 

—91. 1 

-91. 1 

—19.8 

20 

1090 

2 

545-0 

175-I 

175. 1 

47.3. 

21 

1627 

4 

406.7 

-■38-3 

—138.3 

-25.4I 

22 

1122 

2 

561.0 

154.3 

154-3 

37-9 

23 

1798 

4 

449-5 

—III. 5 

—III. 5 

—19.9  V 

6.6 

24 

1202 

2 

601.0 

151-5 

151-5 

33-7 

25 

642 

I 

642.0 

41.0 

41.0 

6.8j 

26 

1401 

3 

467.0 

— 175-0 

—175.0 

—27-3"^ 

27 

1297 

2 

648.5 

181. 5 

181. 5 

38.9 

28 

2215 

4 

553-7 

-94-8 

—94.8 

— 14.6  V 

5-3 

29 

1410 

2 

705-0 

151. 3 

151-3 

27.3 

30 

1439 

2 

719-5 

14.5 

14.5 

2.1  J 

APPENDIX  I 


255 


•GROWTH  OF  RABBITS.      A,  M.M.^S— {Continued) 


Total 

Average 

Increase 

Over  Last 

Measurement 

Average 

Daily 
Increase 

Daily 
Per  Cent. 
Increase 

Age 
Days 

Weight 
Grams 

Obs. 

Av.  Daily 
Per   Cent. 
Increase 

31 

2502 

4 

625.5 

—94.0 

—94.0 

—  13.0 

32 

1530 

2 

765.0 

139-5 

139-5 

22.3 

33 

1564 

2 

7S2.O 

17.0 

17.0 

2.2    > 

3-1 

34 

1575 

2 

787-5 

5-5 

5.5 

-7 

35 

1627 

2 

813.5 

26.0 

26.0 

3-3J 

36 

1683 

2 

841.5 

28.0 

28.0 

3.4  ] 

37 

2914 

4 

72S.5 

— 113.0 

— 113. 0 

—  13.4 

33 

1830 

2 

915.0 

186,5 

186.5 

25.6    >• 

5-5 

39 

1842 

2 

921.0 

6.0 

6.0 

.7 

40 

3108 

4 

777-0 

—144.0 

—144.0 

-I5-6J 

45 

3304 

4 

826.0 

49.0 

9.8 

1.3   1 

50 

2071 

2 

I035-5 

209.5 

41.9 

5.1 

55 

3881 

4 

970.2 

-65.3 

—13. 1 

-1.3    \ 

1.6 

60 

4167 

4 

1041.7 

71-5 

14.3 

1-5 

65 

4465 

4 

1116.2 

74.5 

14-9 

1.4J 

70 

4969 

4 

1242.2 

126.0 

25.2 

2-3  ) 

75 

5519 

4 

1379-7 

137-5 

27-5 

""■Iy 

I.O 

80 

4013 

3 

1337-7 

— 42.0 

-8.4 

-.b[ 

85 

2690 

2 

I345-0 

7.3 

1.5 

.1 } 

90 

95 

3120 

2 

1560.0 

215.0 

21.5 

1.6) 

100 

3195 

2 

1597-5 

37-5 

7-5 

■n 

no 

3555 

2 

1777-5 

180.0 

18.0 

'•o\ 

I.O 

120 

3836 

2 

1918.0 

140.5 

14.0 

.8 ; 

150 

4268 

2 

2134.0 

216.0 

7-2 

A 

165 

4517 

2 

225S.5 

124.5 

8-3 

-4 

180 

4570 

2 

2285.0 

26.5 

1.8 

.1  > 

.3 

195 

4812 

2 

2406.0 

121.0 

8.1 

.4 

210 

4954' 

2 

2477.0 

71.0 

4-7 

.2^ 

Months 

8 

5052 

2 

2526.0 

49.0 

1.6 

.071 

9 

4812 

2 

2406.0 

— 120.0 

—4.0 

-1-3    [ 

—-4 

10 

4795 

2 

2397.5 

-8.5 

—•3 

—.01  ) 

256 


AGE,  GROWTH,  AND  DEATH 


GROWTH  OF  RABBITS.     B,  FEMALES,  NOT  LITTERING 

WHILE  YOUNG 


Total          1 

Average 

Increase 
Over  Last 

Average 
Daily 

Daily 
Per   Cent. 

Av.  Daily 

Age 

Per  Cent. 

Days 

Weight 
Grams 

Obs. 

Measurement 

Increase 

Increase 

Increase 

0 

242.8 

5 

486 

I 

275-9 

5 

55-2 

6.6 

6.6 

13-6^ 

2 

310-3 

5 

62.1 

6.9 

6.9 

12-5 

3 

391-5 

5 

78-3 

16.2 

16.2 

26.1    V 

x6.o 

4 

431-7 

5 

86.3 

8.0 

8.0 

10.2 

5 

507.2 

5 

IOI.4 

15.1 

15-I 

17-5  J 

6 

252.0 

2 

126.0 

24.6 

24.6 

24-2  ^ 

4-4 

7 

657.5 

5 

131-5 

5-5 

5-5 

8 

746.6 

5 

149-3 

17.8 

17.8 

13-5  V 

11.4 

9 

806.5 

5 

161. 3 

12.0 

12.0 

8.0 

10 

866.8 

5 

173-4 

12. 1 

12. 1 

7-1  , 

II 

922.7 

5 

184.5 

II. I 

II. I 

6.4  " 

12 

1012.2 

5 

202.4 

17.9 

17.9 

9-7 

13 

576.0 

2 

288.0 

85.6 

85.6 

42.3    > 

15.3 

14 

1236.5 

5 

247-3 

—40.7 

—40.7 

—14. 1 

15 

653-0 

2 

326.5 

79-2 

79-2 

32.0 

16 

1257.0 

5 

251-4 

—75-1 

—75-1 

—23.0 

17 

1314.0 

5 

262.8 

II. 4 

11.4 

4-5 

18 

783.0 

2 

391.5 

128.7 

128.7 

48.9    > 

10.5 

19 

142 1 

5 

284.2 

—107.3 

—107.3 

—27.4 

20 

850 

2 

425-0 

140.8 

140.8 

49-5  . 

21 

1612 

5 

322.4 

— 102.6 

— 102.6 

-24.1  1 

22 

923 

2 

461.5 

139- 1 

139-I 

43-1 

23 

1785 

5 

357-0 

—104.5 

—104.5 

—22.6    > 

8.4 

24 

992 

2 

496.0 

139.0 

139.0 

38.9 

25 

529 

I 

529-0 

33-0 

33-0 

6-7  j 

26 

1507 

4 

376-7 

—152.3 

—152.3 

—28.8  s 

27 

1098 

2 

549 -o 

172.3 

172.3 

45-7 

28 

2251 

5 

450.2 

—98.8 

-98. 8 

—18.0    > 

6.8 

29 

1203 

2 

601.5 

151-3 

151-3 

33-6 

30 

1222 

2 

611. 0 

9-5 

9-5 

1.6  _ 

31 

2570 

5 

514-0 

—97.0 

—97-0 

—15-9^ 

32 

1313 

2 

656.5 

142.5 

142.5 

27.7 

33 

2670 

5 

5340 

— 122.5 

— 122.5 

—18.7    . 

4.7 

34 

1367 

2 

683-5 

149-5 

149-5 

28.0 

35 

1398 

2 

699.0 

15-5 

15-5 

2.3, 

36 

1461 

2 

730.5 

31-5 

31.5 

4-5  \ 

37 

3073 

5 

614.6 

-115-9 

—  "5-9 

—15.9 

38 

1621 

2 

810.5 

195-9 

195-9 

31-9    > 

.3 

39 

1606 

2 

803.0 

—7.5 

—7-5 

—-9 

40 

3160 

5 

632.0 

— 171. 0 

— 171. 0 

—21.3 

45 

3522 

5 

704.4 

72-4 

14-5 

2.3 

50 

1872 

2 

936.0 

231.6 

46-3 

66 

55 

4039 

5 

807.8 

—128.2 

—25  6 

—2.7 

2.4 

60 

4452 

5 

890.4 

82.6 

16.5 

2.0 

65 

49-8 

5 

980.4 

go.o 

18.0 

2.0  _ 

APPENDIX  I 


257 


GROWTH  OF  RABBITS.     B,  FEMALES    NOT  LITTERING 
WHILE    YO\j:sG— {Continued) 


Age 
Days 

Total 

Average 

Increase 

Over  Last 

Measurement. 

Average 

Daily 
Increase 

Daily 
Per  Cent. 
Increase 

Av.  Daily 

Weight 
Grams 

Obs. 

Per    Cent. 
Increase 

70 

5286 

5 

1057.2 

76.8 

154 

1.6  "] 

75 

5668 

5 

I133.6 

76.4 

15-3 

1.4 

80 

5964 

5 

II92.8 

59-2 

II. 8 

I.O     ]■ 

1 .0 

85 

6362 

5 

1272.4 

79.6 

15.9 

1-3 
—0.1  J 

.     90 

2528 

2 

1264.0 

-8.4 

—1.7 

95 

5839 

4 

1459- 7 

195.7 

39-1 

■■■! 

.9  ( 

100 

4626 

3 

1542.0 

82.3 

16.5 

1.6 

no 

5055 

3 

1685.0 

143.0 

14-3 

320 

5494 

3 

1831-3 

146.3 

14.6 

.9  J 

l^iO 

609+ 

3 

2031.3 

200.0 

6.7 

•4l 
.6 

165 

66S2 

3 

2227.3 

196,0 

I3-I 

iSo 

7134 

3 

237S.0 

150.7 

10.0 

•5    } 

.4 

195 

6934 

3 

2311.3 

—66.7 

—4-4 

.2 

.6  J 

210 

7597 

3 

2532.3 

221.0 

14-7 

Months 

8 

5504 

2 

2752.0 

219.7 

7-3 

•3    ) 

9 

5694 

2 

2b47.o 

95-0 

3.2 

-A 

.1 

10 

5300 

2 

2650.0 

—197.0 

—6.6 

APPENDIX  II,     GROWTH  OF  CHICKENS. 


T^HE  data  which   I  have  collected  concerning  the  growth  of 
*       chickens  have  not  been  published  hitherto,  and  are  there- 
fore  printed   here.      It  was  from  the  percentage  increments  of 
these  tables  that  Figures  33  and  34  were  constructed. 
GROWTH  OF  CHICKENS.     A,  MALES 


Age 
Days 

Total 

Average 

Increase 

Over  Last 

Measurement 

Average 

Daily 
Increase 

Daily 

Per  Cent. 

Increase 

Av.  Daily 

Weight 

Obs. 

Per   Cent. 
Increase 

Grams 

I 

93 

2 

46.5 

2 

92 

2 

46.0 

—  ■5 

—•5 

—  I.I'^ 

3 

95 

2 

47-5 

1-5 

1-5 

3.3    I 

3-9 

4 

103 

2 

51-5 

4.0 

4.0 

8-4  I 
4-9J 

5 

108 

2 

54.0 

2.5 

2.5 

6 

120 

2 

60.0 

6.0 

6.0 

II. i'^ 

7 

137 

2 

68.5 

8.5 

8-5 

14.2 

8 

139 

2 

69.5 

I.O 

1.0 

1.5  y 

9.0 

9 

146 

2 

73-0 

3-5 

3-5 

5.2 

10 

165 

2 

82.5 

9-5 

9-5 

I3-0  J 

ir 

180 

2 

go.o 

7-5 

7-5 

9.0 

12 

187 

2 

93-5 

3-5 

3-5 

3-9 

13 

189 

2 

94-5 

1.0 

1.0 

I.I   > 

6.0 

14 

207 

2 

I03-5 

9.0 

9.0 

9-5 

15 

220 

2 

IIO.O 

6.5 

6.5 

6-3J 

16 

255 

2 

127-5 

17.5 

17-5 

15-9^ 

17 

248 

2 

124.0 

—3-5 

—3-5 

—2.7 

iS 

26S 

2 

134.0 

lO.O 

10,0 

8.1   [ 

6.5 

19 

288 

2 

144.0 

10. 0 

10. 0 

7.5 

20 

298 

2 

149.0 

5-0 

5-0 

3-5J 

21 

316 

2 

158.0 

9.0 

9.0 

6.0    ^ 

22 

320 

2 

160.0 

2.0 

2.0 

1-3 

5-1 

23 

346 

2 

1730 

13.0 

13.0 

8.1  ) 

24 

25 

26 

27 

399 

2 

199-5 

26.5 

6.6 

3.8] 
4.8  [ 

28 

418 

2 

209.0 

9-5 

9-5 

3-7 

29 

422 

2 

211. 0 

2.0 

2.0 

.9  r 
5-2J 

30 

444 

2 

222.0 

II. 0 

II. 0 

258 


APPENDIX  II 


259 


GROWTH  OF  CHICKENS.     A,   UKLY.S— {Continued) 


Age 

Total 

Average 

Increase 
Over  Last 

Average 
Daily 

Daily 
Per  Cent. 

Av.  Daily 

Days 

Weight 
_      Grams 

Per  Cent. 

Obs 

Measurement 

Increase 

Increase 

Increase 

31 

494 

2 

247.0 

25.0 

25.0 

"■3l 

32 

524 

2 

262.0 

15-0 

15.0 

6.1 

33 

533 

2 

266.5 

4.5 

4.5 

1.7    > 

5-2 

34 

564 

2 

282.0 

15.5 

15.5 

5-8 

35 

570 

2 

285.0 

3-0 

3.0 

i.i^ 

36 

600 

2 

300.0 

15-0 

15.0 

5-3^ 
i.o 

37 

606 

2 

303.0 

3.0 

3.0 

38 

661 

2 

330.5 

27.5 

27.5 

9.1    > 

4.2 

39 

662 

2 

331.0 

■5 

•5 

.1 

40 

700 

2 

350.0 

19.0 

19.0 

5-7. 

42 

737 

2 

368.5 

18.5 

9.2 

2.6^ 

44 

788 

2 

394.0 

25.5 

12.7 

3-4 

46 

815 

2 

407.5 

13  5 

6.7 

.8    > 

2.2 

48 

849 

2 

424.5 

17.0 

8.5 

2.1 

50 

881 

2 

440.5 

16.0 

8.0 

1.9^ 

52 

926 

2 

463.0 

22.5 

II. 0 

2.5    ' 

54 

984 

2 

492.0 

29.0 

14.5 

3.1 

56 

v 

2.7 

58 

60 

1127 

2 

563.5 

71.5 

II. 9 

2.4   j 

62 

1194 

2 

597.0 

33-5 

16.7 

2.9   \ 

64 

1182 

2 

591.0 

~6.o 

— 3.0 

— .5 

66 

1297 

2 

648.5 

57-5 

28.7 

4.8    V 

2.8 

68 

1318 

2 

659.0 

10.5 

5.2 

.8 

70 

1400 

2 

7ou,o 

41.0 

20.5 

3.1    J 

72 

74 

1552 

2 

776.0 

76.0 

19.0 

2.7     1 

76 

/ 

78 

\ 

2.1 

80 

1692 

2 

846.0 

70.0 

II.7 

1.5     ) 

82 

i'S53 

2 

926.5 

80.5 

40.2 

4.7    1 

86 

1974 

2 

987.0 

60.5 

15. 1 

1.6 

90 

2056 

2 

1028.0 

41.0 

10.2 

1.0     V 

94 

2.3 

98 

2408 

2 

1204.0 

176.0 

22.0 

2.1    j 

102 

2705 

2 

1352.5 

14S.5 

37-1 

"     [ 

106 

2783 

2 

1391.5 

39-0 

9-7 

1.5 

no 

2869 

2 

1434.5 

43-0 

10.7 

.8    S 

120 

3185 

2 

1592.5 

158.0 

15.8 

I.I    ■^ 

125 

3450 

2 

1725.0 

132.5 

26.5 

1.7 

130 

3452 

2 

1726.0 

I.O 

.2 

.1     V 

1.0 

13s 

3636 

2 

1818.0 

92.0 

18.4 

I.I 

140 

3840 

2 

1920.0 

102.0 

20.4 

I.I    J 

192 

4897 

2 

2^48.5 

528.5 

10.2 

•5    1 

197 

5025 

2 

2512.5 

64.0 

12.8 

•5     - 

-3 

202 

4965 

2 

2482.5 

— 30.0 

—6.0 

-.2    j 

335 

5552 

2 

2776.0 

293-5 

2.2 

.09  \ 
.02  )■ 

341 

5559 

2 

2779-5 

3-5 

.6 

.1 

351 

5475 

2 

2737-5 

—42.0 

—4.2 

—.1    3 

26o 


AGE,  GROWTH,  AND  DEATH 


GROWTH   OF 

CHICKENS. 

B,    FEMALES 

Total 

Increase 

Average 

Daily 

Age 

Av.  Daily 

Days 

Weight 

Average 

Over  Last 

Daily 

Per  Cent. 

Per  Cent. 

Grams 

Obs. 

Measurement 

Increase 

Increase 

Increase 

0 

39 

I 

39 

I 

326 

8 

40.7 

2 

321 

8 

40.1 

—.6 

—.6 

—1-5    ) 

3 

330 

8 

41.2 

I.I 

I.I 

2.7    f 

4 

352 

8 

44.0 

2.8 

2.8 

6.8  r 

4.2 

5 

383 

8 

47-9 

3-9 

3.9 

8.9  ) 

6 

419 

8 

52.4 

4  5 

4.5 

9-4    1 

7 

468 

8 

58.5 

6.1 

6.1 

II. 6 

8 

475 

8 

59-4 

•9 

■9 

1-5     } 

8.6 

9 

504 

8 

63.0 

3.6 

3-6 

6.1 

lO 

577 

8 

72.1 

9-1 

9.1 

14.4   j 

II 

610 

8 

76.2 

4.1 

4.1 

5.7    ^ 
3-8 

12 

633 

8 

79.1 

2.9 

2.9 

13 

668 

8 

83.5 

4-4 

4.4 

5.6     } 

5-8 

14 

710 

8 

88.7 

5-2 

5-2 

6.2 

15 

764 

S 

95-5 

6.8 

6.8 

7.7    J 

i6 

880 

8 

IIO.O 

14-5 

14-5 

15-2     ^ 

17 

876 

8 

109.5 

—.5 

—•5 

—•5 

i8 

938 

8 

117. 2 

7-7 

7-7 

7.0     } 

7.1 

19 

995 

8 

124.4 

7.2 

7.2 

6.1 

20 

1071 

8 

133-9 

9-5 

9-5 

7.6   j 

21 

1116 

8 

139-5 

5-6 

5-6 

4.2    ) 

22 

1139 

8 

142.4 

2.9 

2-9 

2.1     I 

5.0 

23 

1082 

7 

154.6 

12.2 

12.2 

8.6    ) 

24 

25 

26 

144 

I 

144.0 

— 10.6 

—3-5 

—2.3    1 

27 

1356 

8 

169.5 

25-5 

25-5 

17-7 

28 

1416 

8 

177.0 

7-5 

7.5 

4-4     } 

5-4 

29 

1448 

8 

181. 0 

4.0 

4.0 

2.3 
4.9    j 

30 

1519 

8 

189.9 

8.9 

8.9 

31 

1656 

8 

207.0 

17. 1 

17. 1 

9.0   \ 

32 

1733 

8 

216.6 

9.6 

9.6 

4.6 

33 

17S7 

8 

223.4 

6.8 

6.8 

3.1     > 

5-5 

34 

1908 

8 

238.5 

I5-I 

I5-I 

6.8 

35 

1985 

8 

248.1 

Q.6 

9.6 

4.2    J 

36 

2057 

8 

257.1 

9.0 

9.0 

3-6    ^ 

37 

2114 

8 

264.2 

7-1 

7-1 

2.8 

38 

2254 

8 

281.7 

17.5 

17-5 

6.6     K 

3-8 

39 

2303 

8 

287.9 

6.2 

6.2 

2.2 

40 

2394 

8 

299.2 

ir-3 

II-3 

3.9    J 

42 

2572 

8 

321.5 

22.3 

III 

3.7    \ 

44 

2742 

8 

342.7 

21.2 

10.6 

3-3 

46 

2841 

8 

355-1 

12.4 

6.2 

1.8     V 

2.5 

48 

2634 

7 

376.3 

21.2 

10.6 

3-0 

50 

3064 

8 

383-0 

6.7 

3-3 

•9   J 

APPENDIX   II  261 

GROWTH  OF  CHICKENS.     B.  YENiA'LY.'n-yContimird) 


Total 

Daily 
Per  Cent. 
Increase 

Av.  Daily 
Per   Cent. 
Increase 

Age 
Days 

Weight 

Obs. 

Average 

Over  Last 
Measurement 

A  V eragc 

Daily 
Increase 

Grams 

52 

3209 

8 

401. 1 

18. 1 

9.0 

2.3    1 

54 
56 

3430 

8 

428.7 

27,6 

13-8 

3-4 

34 

58 

426 

I 

426.0 

—2.7 

—.7 

— .  I 

8.2    ^ 

60 

3973 

8 

496.6 

70.6 

35-3 

62 

4255 

8 

531-9 

35-3 

17.6 

3.5  s 

64 

4274 

8 

534-2 

2.3 

I.I 

.2 

2.4 

66 

4639 

8 

579-9 

45-7 

22.8 

4-3      =■ 

68 

4861 

8 

607.6 

27.7 

13.8 

2-4 

70 

72 
74 

5021 

8 

627.6 

20.0 

10. 0 

1.6   j 

5538 

8 

692.2 

64.6 

16. 1 

2.4    \ 

76 

i 

2-5 

78 

707 

I 

707.0 

14.8 

3-9 

•5     \ 

80 

5398 

7 

771. 1 

64.1 

32.0 

4.5     ) 

82 

6592 

8 

824.0 

52.9 

26.9 

3-4     1 

86 

6924 

8 

865.5 

41-5 

10.4 

1.2 

1.7 

90 

7093 

8 

886.6 

21. 1 

5-3 

.5     \ 

94 

98 

8173 

8 

1021.6 

13s. 0 

l6.g 

19    J 

102 

8981 

8 

1122.6 

lOI.O 

25.2 

2.5  ) 

1.6  I 

106 

9552 

8 

JI94-0 

71-4 

17.8 

1-5 

110 

9742 

8 

1217.7 

23-7 

5.9 

.5  s 

115 

120 

10593 

8 

1324-1 

106.4 

10.6 

■9    1 

125 

9831 

7 

1404.4 

80  3 

16. 1 

.8 

130 

1 1492 

8 

1436-5 

32.1 

6.4 

135 

12087 

8 

1510.9 

74  4 

14.9 

I.O 

.6    j 

140 

12456 

8 

1557-0 

46.1 

9  2 

192 

15786 

8 

1973.2 

416.2 

8.0 

•5     ) 

•5 

197 

16546 

8 

2068.2 

950 

19.0 

1.0 

202 

16551 

8 

2068.9 

.7 

.1 

.00  ) 

335 

17276 

8 

2159  5 

90.6 

.7 

•03  ) 

341 

16985 

8 

2123. I 

—36-4 

—6.1 

-•3     \ 

.  2 

351 

17535 

8 

2191.9 

68.8 

69 

.3     ) 

APPENDIX  III.     DEATH  OF  PROTOZOA 

IN  1877  I  pointed  out  that  a  Protozoon  cannot  be  directly  com- 
'  pared  with  a  Metazoan  ^^Proceedings  Boston  Society  of  Natural 
History^  April  i8th,  p.  170),  and  in  1879  formulated  this  opinion 
more  clearly.  Since  each  Metazoon  consists  of  many  successive 
generations  of  cells,  it  really  is  a  cell  cycle,  and  can  only  be 
homologised  with  a  cycle  of  protozoan  generations,  not  with  any 
single  Protozoon,  which  is  but  a  single  cell.  Hence  it  follows 
that  the  death  of  an  individual  Protozoon  is  not  homologous  with 
the  death  of  an  individual  multicellular  animal. 

Weismann  committed  the  fundamental  error  of  assuming  the 
complete  homology  of  the  two  forms  of  death,  and  thus  reached 
the  false  conclusion  that  Protozoa  are  all  certainly  potentially 
immortal.  The  error  is  all  the  more  important  because  without 
assuming  its  truth  the  whole  speculative  structure  of  germ 
plasm  hypotheses  cannot  stand.  As  Oskar  Hertwig  has  already 
expounded  in  the  first  part  of  his  Zeit  und  Streitfragen  the  de- 
pendence of  Weismann's  "  Keimplasm  "  doctrines  upon  the 
incorrect  hypothesis  of  Protozoon  immortality,  it  is  unnecessary 
to  discuss  the  matter  further. 

Concerning  Weismann's  notions  about  death  a  few  words  may 
be  added.  His  view  was  first  published  in  1882,  in  his  essay 
Ueber  die  Dauer  des  Lebens,  and  it  has  been  again  advocated  in 
his  article  Ueber  Leben  und  T^'a:' (1884),  and  has  been  defended 
by  him  subsequently.'  Weismann  missed  the  real  problem,  which 
is  whether  Protozoa  like  Metazoa  develop  in  senescent  cell  cycles. 
My  position  is  unchanged,  and  is  clearly  presented  by  the 
following  quotation  from  an  article  in  the  American  Naturalist : 

"  He    [Weismann]    misses   the  real    problem.     The  following 

'  E.  g  ,  Biologlsclies  CfutralblaU.,  iv.,  p.  690. 

262 


APPENDIX  HI  263 

reasoning  leads  to  this  decision.  Protozoa  and  Metazoa  consist 
of  successive  generations  of  cells  ;  in  the  former  the  cells  sep- 
arate ;  in  the  latter  they  remain  united  ;  the  death  of  a  Protozoon 
is  the  annihilation  of  a  cell,  but  the  death  of  a  Metazoon  is 
the  dissolution  of  the  union  of  cells.  Such  a  dissolution  is  the 
result  of  time,  that  is  to  say,  of  the  period  necessary  to  the 
natural  duration  of  life,  and  we  call  it,  therefore,  '  natural 
death.'  Moreover,  we  know  that  natural  death  is  brought  about 
by  gradual  changes  in  the  cells  until,  at  last,  certain  cells,  which 
are  essential  to  the  preservation  of  the  whole,  cease  their  func- 
tions. Death,  therefore,  is  a  consequence  of  changes  which 
progress  slowly  through  successive  generations  of  cells.  These 
changes  cause  senescence,  the  end  of  which  is  death.  If  we  wish 
to  know  whether  death,  in  the  sense  of  natural  death,  properly  so 
called,  occurs  in  Protozoa  or  not,  we  must  first  possess  some  mark 
or  sign,  by  which  we  can  determine  the  occurrence  or  absence  of 
senescence  in  unicellular  organisms. 

"Around  this  point  the  whole  discussion  revolves.  Certainly 
a  simpler  and  more  certain  conclusion  could  hardly  be  drawn 
than  that  the  death  of  a  Metazoon  is  not  identical,  i.e.,  homol- 
ogous, with  the  death  of  a  single  cell.  Weismann  tacitly  assumed 
precisely  this  homology,  and  bases  his  whole  argument  on  it. 
In  all  his  writings  upon  this  subject,  he  regards  the  death  of  a 
Protozoon  as  immediately  comparable  with  the  death  of  a  Meta- 
zoon. If  we  seek  from  Weismann  for  the  foundation  of  this  view 
we  shall  have  only  our  labour  for  our  pains.  Starting  from  this 
view  Weismann  comes  to  the  strictly  logical  conclusion  that  the 
Protozoa  are  immortal.  This  is  a  paradox  !  In  fact,  if  one 
compares  death  in  the  two  cases,  from  Weismann's  standpoint, 
then  we  must  assume  a  difference  in  the  causes  of  death,  and 
conclude  that  the  cause  in  the  case  of  the  Protozoa  is  external 
only,  while  in  the  Metazoa  it  is  internal  only,  for,  of  course,  we 
may  leave  out  of  account  the  accidental  deaths  of  Metazoa.  If 
we  approach  the  problem  from  this  side,  we  encounter  the 
following  principal  question  :  Does  death  from  inner  causes 
occur  in  Protozoa  ?      Weismann  gives  a  negative  answer  to  this 


2  64  AGE,  GROWTH,  AND  DEATH 

question,  with  his  assertion  that  unicellular  organisms  are  im- 
mortal. The  assertion  remains,  but  the  proof  of  the  assertion 
is  lacking.  In  order  to  justify  the  assertion,  it  must  be  demon- 
strated that  there  does  not  occur  in  Protozoa  a  true  senescence, 
showing  itself  gradually  through  successive  generations  of  cells. 
Has  Weismann  furnished  this  demonstration?  Certainly  not. 
He  has,  strictly  speaking,  not  discussed  the  subject.  It  is  clear 
that  we  must  first  determine  whether  natural  death  from  senes- 
cence occurs  in  Protozoa  or  not,  before  we  can  pass  to  a  scientific 
discussion  of  the  asserted  immortality  of  unicellular  beings. 
The  problem  cannot  be  otherwise  apprehended.  Weismann  has 
not  thus  conceived  it,  therefore  the  judgment  stands  against 
him  :  he  misses  the  real  problem" 

E.  Maupas'  has  maintained  that  among  unicellular  animals 
loss  of  vitality  (senescence)  and  actual  rejuvenation  could  be 
demonstrated.  He  was  the  first  to  follow  a  colony  of  Protozoa 
through  a  long  series  of  generations  with  a  view  to  determining 
the  changes  in  the  life  cycle.  His  conclusion  is  that  there  is  an 
actual  exhaustion  of  the  cells  going  on  with  the  progress  of  the 
generations,  and  that  conjugation  must  occur  to  effect  "  rejeu- 
nissement  "  (rejuvenescence)  otherwise  the  cells  of  the  cycle  die 
off.  Similar  experiments  have  been  made  in  this  country  by 
G.  N.  Calkins,'  who  likewise  concludes  that  the  development  of 
Protozoa  is  cyclical,  the  end  of  the  cycle  coming  through  senile 
degeneration  of  the  cells,  and  new  cycles  beginning  by  a  re- 
juvenation effected  by  conjugation.  If  these  conclusions  are 
correct  we  must  expect  to  find  proof  of  cyclical  development  in 
other  Protozoa. 

Maupas  and  Calkins  leave  a  fundamental  question  undecided. 

'  E.  Maupas,  Archives  de  Zool.  Expcr.,  i.,  299  ;  i.,  i\il  (1883)  ;  vi.,  165 
(1888)  ;  vii.,  149(1880). 

^  G.  N.  Calkins,  "  Studies  in  the  Life  History  of  Protozoa,"  Arch.  fur.  Eii- 
tivickelungs  mechanik,  xv.,  139-186,  also  Biol.  Bulletin,  iii.,  192-205,  and 
Journ.  Exp.  Zool.,  i.,  423-461  (1904).  A  compreliensive  and  later  presentation 
of  Calkins's  views  on  the  protozoan  life  cycle  is  given  by  him  in  chapter  xvii. 
of  the  first  volume  of  Osier's  Modern  Medicine  (1907);  see  especially  pp. 
361-367. 


APPENDIX  in  265 

If  it  be  admitted  that  the  mark  of  senescence  in  the  Metazoa  is 
increase  in  the  proportion  of  protoplasm,  and  the  mark  of  reju- 
venation increase  of  the  nuclei,  then  we  must  expect  similar 
variations  in  the  protozoa,  if  there  be  true  senescence  and  re- 
juvenation among  them.  It  is  probable  that  the  observations  to 
decide  this  question  can  be  made  without  serious  difficulty, 
and  indeed  I  think  they  will  soon  be  successfully  accomplished. 

Professor  Richard  Hertwig  has  also  developed  views  concern- 
ing the  death  of  Protozoa,  which  are  certainly  interesting,  sug- 
gestive, and  important  and  have  been  summarised  by  the  author 
in  a  special  article.'  He  accepts  the  views  of  Calkins  as  to 
''''depression"  among  Protozoa,  but  thinks  that  a  further  explanation 
is  necessary  to  explain  senescence  among  Metazoa.  I  quote 
from  p.  23  of  reprint :  "  Die  Teilungsfahigkeit  der  Zellen  eines 
ausgewachsenen  Menschen  oder  Tieres  ist  also  nicht  erloschen, 
sie  ist  nur  nicht  im  Stande  sich  zu  betatigen  ;  sie  ist  zuriick- 
gehalten.  .  .  .  Mit  anderen  worten  die  Zellen  eines  hoch- 
entwickelten  Tieres  teilen  sich  nicht,  weil  sie  den  Wachsthums- 
gesetzen  des  Ganzen  unterworfen  sind,  wie  ein  jeder  von  uns  den 
Gesetzen  des  Staates."  I  agree  with  Professor  Hertwig  that  the 
inhibition  of  growth  plays  an  extremely  important  role  in  the 
higher  animals,  but  as  this  whole  volume  argues,  I  think  that 
cytomorphosis  produces  true  senescence  of  individual  cells,  and 
that  this  senescence  is  more  fundamental  and  essential  than  the 
inhibitory  control. 

The  paper  by  M.  Hartmann^  on  Death,  I  have  not  seen. 
From  a  review  of  it  in  the  Zoologisches  Ceiitralblatt.,  1907,  543,  I 
infer  that  he  has  revived  the  idea  that  reproduction  is  the  cause 
of  death.  He  is  said  to  maintain  that  natural  death  does  occur 
among  the  protozoa.  The  review  cited  says:  "Das  Resultat  seiner 
Erorterungun  fasst  unser  Autor  dahin  zusammen  dass  alien  Pro- 
tozoeii  (Protisten  ueberhaupt)'ein  natiirlicher  Tod  zukommt  und 
dieser  ausnahmslos  mit  der  Fortpflanzung  zusammenfallt." 

'  R.  Hertwig,  "Uber  die  Ursache  des  Todes,"  Beilage  zur  Allgemeinen  Zci~ 
tung,  Dez.  12  u.  13,  igo6. 

^  M.  Hartmann,   Tod  und Fortpflatiztitig,  Miinchen,  igo6. 


APPENDIX  IV.     LONGEVITY  OF  ANIMALS 

A  UGUST  WEISMANN  in  his  essay  on  Lebensdauer  has  col- 
**•  lected  many  data  in  regard  to  the  longevity  of  animals. 
It  is  by  far  the  best  compilation  of  the  sort  known  to  me. 

Mr.  F.  A.  Lucas,  Curator  of  the  Brooklyn  Museum,  has  given 
me  some  additional  facts,  and  by  his  courtesy  I  am  allowed  to 
publish  the  following  quotation  from  a  letter  which  he  addressed 
to  me  on  November  27,  1907: 

"So  far  as  we  know  the  Aldabra  tortoises  have  reached  the 
greatest  age — from  ninety  to  one  hundred  and  fifty  years.  Of 
this  we  may  be  positive.  Carp  'are  said'  'to  have  lived  over  a 
hundred  years,'  and  I  should  not  be  surprised  if  this  were  true. 
I  doubt  much  if  any  mammals  attain  such  an  age.  Until  I  went 
to  Newfoundland  in  1903  I  had  credited  the  whale  with  living  to 
a  very  great  age,  but  my  examination  of  the  many  specimens  I 
saw  there  leads  me  to  doubt  this.  I  discussed  the  matter  a  little 
in  Nature  and  in  Science,  but  the  gist  of  the  matter  is  this — if 
whales  lived  indefinitely  there  should  be  an  indefinite  number  of 
sizes,  whereas  the  animals  fall  into  comparatively  few  groups  as 
regards  size,  and  I  now  doubt  if  the  whale  lives  much  more  than 
twenty-five  years,  though  this  is  a  mere  guess.  Observations 
made  on  the  Pribilof  Islands  during  the  past  ten  years  show  that 
the  fur  seals  probably  do  not  reach  the  age  of  twenty  years  with 
which  they  have  been  credited  and  the  fur  seal  is  a  fairly  large 
mammal.  Even  in  regard  to  reptiles,  which  have  been  supposed 
to  grow  very  slowly  and  almost  indefinitely,  recent  observations 
have  shown  that  the  Galapagos  tortoise  and  our  own  alligator 
may  grow  quite  rapidly." 


266 


APPENDIX    V.      THEORY  OF  LIFE 

T'^HE  abstract  of  the  paper  on  the  theory  of  life,  referred  to  on 
*  p.  viii.,  is  here  reprinted  because  it  still  indicates  the  starting 
point  of  the  studies,  the  results  of  which  are  given  in  the  current 
volume.  So  little  have  we  gained  since  1S79  i^^  ^^^  comprehen- 
sion of  the  basic  phenomena  of  living  things  that  were  I  to  rewrite 
the  abstract  in  accordance  with  present  knowledge  I  should  not 
change  it  essentially.  The  vitalistic  hypothesis  still  seems  to  me 
scientifically  the  best. 

On  the  Conditions  to  be  Filled  by  a  Theory  of  Life.     By 
Charles  Sedgwick  Minot,  of  Boston,   Mass. 

[abstract.] 

It  has  been  so  often  asserted  that  the  essential  nature  of  life 
cannot  be  discovered  by  man,  that  the  remark  has  become 
commonplace.  It  would  seem  that  this  assertion  is  merely  the 
assumption  of  haste,  and  is  based  only  upon  our  present  igno- 
rance of  vital  properties.  It  should  rather  be  said  that  the  main 
object  of  all  botanical  and  zoological  studies  is  ultimately  to  dis- 
cover the  vital  principle.  The  conviction  that  such  is  the  end  of 
biological  research  has  led  me  for  several  years  past  to  endeavour 
to  sort  out  those  vital  phenomena  which  are  most  universal,  in 
order  to  determine  what  are  the  principal  and  essential  functions 
of  living  bodies.  Such  a  labour  cannot  add  much  that  is  new  to 
science,  but  it  forced  me  to  the  conclusion  that  the  favourite 
speculations  of  the  present  time  concerning  the  origin  and  nature 
of  life  as  explained  by  science  were  superficial  and  even  crude, 
principally  because  they  were  not  based  upon  a  careful  examina- 
tion of  the  phenomena  to  be  explained.     In  order  to  avoid  erro- 

267 


268  AGE,  GROWTH,  AND  DEATH 

neous  opinions  I  have  deferred  publication  for  a  long  time,  during 
which,  however,  no  very  essential  improvement  of  the  outline  I 
had  drawn  has  occurred  to  me.  To  deal  with  such  difficult  and 
dangerous  questions  with  complete  success  requires  more  know- 
ledge and  judgment  than  I  possess  ;  I  hope,  therefore,  to  be  al- 
lowed to  publish  what  follows  rather  as  opinions  I  deem  plausible, 
than  as  conclusions  I  believe  certain.  Of  one  thing,  however,  I 
feel  sure — that  it  is  useless  to  discuss  the  opposing  claims  of  con- 
scious automatism,  the  mechanical  theory  of  life  and  a  vital  prin- 
ciple, until  we  decide  what  are  really  the  vital  phenomena  to  be 
explained. 

All  the  higher  animals  and  plants  are  known  to  consist  of  col- 
onies of  cells.  There  are  beside  many  unicellular  animals  and 
plants.  Of  late  years  there  have  been  described  a  large  number 
of  organisms  stated  to  consist  solely  of  protoplasm.  It  is  on  these 
discoveries  that  the  various  protoplasm  theories  of  life  have  been 
founded.  Many  popular  articles  have  been  written  beginning 
with  the  assertion  that  protoplasm  is  a  simple,  jelly-like  mass, 
and  ending  with  the  conclusion  that  life  depends  solely  on  the 
mechanical  properties  of  protoplasm.  I  think  it  cannot  be  too 
seriously  regretted  that  respectable  periodicals  have  published  so 
many  of  such  articles,  because  all  but  the  ignorant  know  that 
protoplasm  is  not  jelly-like,  and  not  simple  ;  on  the  contrary,  it 
consists  of  many  and  various  chemical  compounds,  and  from 
recent  investigations  it  has  become  probable  that  it  never  exists 
as  a  homogeneous  mass,  but  always  contains  numerous  vacuoles, 
each  enclosing  some  distinct  substance  or  substances,  liquid  or 
solid  ;  this  structure  explains  the  appearance  of  the  so-called 
protoplasmatic  network.  Moreover,  protoplasm  probably  can- 
not permanently  maintain  its  life  when  separated  from  a  nucleus.' 
The  number  of  protoplasmatic  animals  supposed  to  be  without 
nuclei  has  rapidly  diminished, — especially  as  the  nucleus  of  the 

1  By  this  I  mean  only,  that  all  vital  functions  cannot  be  performed,  because 
to  some  of  them  the  nucleus  is  necessary.  Of  course  protoplasm  may  remain 
alive  when  separated  from  the  nucleus,  but  the  possibility  of  reproduction  is 
probably  lost. 


APPENDIX  V  269 

Foraminiferje  has  been  discovered,  and  the  unicellular  nature  of 
the  Infusoria  established.  To  say  that  all  the  supposed  proto- 
plasmatic animals  have  a  nucleus  is  not  yet  safe,  but  it  must  not 
be  forgotten  that  in  many  cases  the  nucleus  is  discoverable  when 
properly  searched  for  with  the  aid  of  nice  histological  methods, 
and  that  those  cases  where  it  has  not  been  found  as  yet  are  all 
cases  of  uncertainty,  partly  because  careful  observations  have  not 
been  made,  partly  because  the  objects  themselves  are  too  minute. 
The  probability,  therefore,  is  against  the  separate  existence  of 
protoplasm,  and  is  in  favour  of  the  universal  presence  of  the 
nucleus.  This  view  is  strengthened  by  the  discovery  of  the  real 
nature  of  Bathybius. 

A  cell  must,  therefore,  be  regarded  as  the  unit  of  life,  and  the 
problem  we  are  considering  becomes  to  determine  the  general 
properties  and  functions  of  cells.  I  reason  chiefly  upon  the  basis 
of  zoology,  that  branch  of  biology  which  alone  I  have  studied 
scientifically.  The  principal  peculiarities  of  cells,  as  thus  deter- 
mined, I  consider  to  be  as  follows  : 

1.  Irritability.  When  some  motion  strikes  the  cell  it  may 
simply  act  mechanically  or  give  rise  to  peculiar  effects  which  oc- 
cur only  in  living  matter.  Nothing  but  some  mode  of  motion 
ever  acts  as  a  stimulus.  The  effect  produced  by  stimuli  is  a  sen- 
sation. The  stimuli  may  come  from  the  outside  or  from  the  in- 
side of  the  cell.  The  ultimate  effects  of  the  irritation  may  be 
inhibited,' — that  is  delayed  or  prevented  by  the  cell  itself. 

2.  The  power  of  doing  work,  or  developing  in  response  to  a 
stimulus,  or  from  some  other  cause,  a  certain  amount  of  motion 
or  energy.  The  work  done  may  be  mechanical,  electrical,  calo- 
rific, or  even  luminiferous.  The  power  of  doing  work  cannot 
be  sustained  indefinitely,  hence  the  phenomena  of  fatigue  or 
exhaustion,  and  recovery. 

3.  To  set  free  energy  by  chemical  changes;  each  cell  must  be 
supposed  to  maintain  a  vortex  by  which  matter  is  continually 
drawn  in  from  the  outside,  the  elements  re-combined,  and 
finally  in  part  ejected,  while  the  shape  of  the  vortex  or  cell  is 
preserved. 


2  70  AGE,  GROWTH,  AND  DEATH 

4.  Grozuih.  The  cell  retains  permanently  a  portion  of  the 
matter  drawn  in  by  the  vortex. 

5.  Multiplication.  The  cell  cannot  grow  beyond  a  certain 
limit,  but  instead  of  further  enlargement  it  divides.  (The  bud- 
ding of  Infusoria  is  only  a  peculiar  form  of  cell  division.) 

6.  Senescence.  With  each  successive  generation  of  cells  the 
power  of  growth  diminishes.  Were  this  otherwise,  the  growth 
of  each  individual  at  any  given  time  would  be  in  geometrical 
progression.     This  loss  of  power  I  term  senescence. 

7.  Rejuvenation.  The  effects  of  senescence  are  overcome  by 
some  of  the  cells  separating  in  character  from  the  rest,  and 
giving  rise  to  peculiar  bodies,  the  eggs  and  spermatozoa.  A  new 
cycle  of  cell  generations  is  thus  formed.  In  each  cycle  there  is  a 
slow  senescence  terminating  in  the  formation  of  a  new  cycle  by 
the  rejuvenating  influence  of  the  sexual  products. 

8.  Material  continuity  of  life.  The  actual  continuity  of  living 
matter  is  unbroken  in  consequence  of  the  nature  of  cell  division 
and  of  the  origin  of  the  sexual  products.  We  cannot,  therefore, 
yet  conceive  the  origin  of  life,  especially  as  all  attempts  to 
demonstrate  spontaneous  generation  have  been  unconvincing. 

9.  Heredity.  Every  cell  inherits  the  qualities  of  its  parents, 
though  imperfectly.  The  resemblance  of  an  animal  to  its  parent 
is  due  to  the  fact  that  a  given  cell  of  the  parent  cycle  transmits 
an  influence  to  the  child  cycle,  tending  to  cause  a  similar  cell  to 
be  developed  in  the  same  place  and  at  the  same  time  in  the  off- 
spring. Heredity  is  imperfect,  both  inherently  and  from  the 
effects  of  external  circumstances. 

10.  Direct  influence  of  external  circumstances.  This  has  now 
become  established  in  several  cases. 

11.  Predetermined  union  of  cells.  When  the  cells  of  one  cycle 
unite  to  form  an  animal,  they  arrange  themselves  definitely  in 
three  sets  (germ  layers),  at  least  in  the  higher  metazoa. 

12.  Vital  union  of  cells.  Some  of  the  cells  of  each  set  are 
united  by  means  of  the  nerves  into  a  common  neural  union  or 
association,  each  member  of  which  loses  some  of  its  originality  and 
independence  as  an  individual  cell,  and  becomes  able  to  affect  the 


APPENDIX  V  ■  271 

other  members  of  the  union  both  in  their  growth,  nourishment, 
and  sensations. 

13.  Teleological  mechanism.  This  principle  has  been  recently 
clearly  formulated  by  Pfliiger — a  need  causes  its  own  satisfaction, 
e.g.^  the  need  of  digestion  produced  by  the  presence  of  food 
causes  the  secretion  of  the  digestive  fluids. 

14.  Memory.  Man  knows  by  introspection  that  he  has  mem- 
ory; we  attribute  it  to  the  higher  animals  by  common  consent, 
and  there  is  no  reason  for  denying  its  existence  in  the  lower 
forms.  Real  memory  implies  consciousness,  otherwise  it  cannot 
be  known  that  the  sensation  refers  to  the  past. 

15.  Habit.  This  may  be  best  defined  as  unconscious  memory. 
It  seems  to  me  a  grave  error  to  identify  habit  and  real  memory. 
Habit  implies  that  acts  become  easier  if  repeated. 

16.  Consciousness.  Our  knowledge  of  this,  as  of  memory,  is 
introspective,  and  is  attributable  to  animals  for  the  same  reasons. 

17.  Free  will.  If  there  be  such  a  thing  it  must  of  course  be 
entered  here. 


^These  are  the  essential  categories  of  the  phenomena  of  animal 
life,  and  as  they  are  all  performed  by  colonies  of  cells,  they  must 
be  the  work  of  the  units  of  such  colonies,  or  in  other  words  each 
one  of  these  properties  is  that  of  a  cell.  There  are  reasons  for 
thinking  that  unicellular  animals  have  the  same  properties.  To 
summarise,  every  cell  performs  all  functions  : 

1.  Responds  to  stimuli. 

2.  Maintains  the  vortex. 

3.  Grows  and  divides. 

4.  Inherits,  varies,  and  bequeaths. 

Further,  each  cell  probably  has 

5.  A  sexual  power,  usually  dormant. 

6.  Consciousness. 

7.  Memory. 

8.  Habit. 


5  72  AGE,  GROWTH,  AND  DEATH 

To  explain  life  we  must  discover  why  it  displays  itself  only  in 
a  physical  basis  composed  of  various  albumenoid  molecules, 
imbibed  with  water  and  certain  salts,  and  commingled  with  other 
complex  organic  compounds,  all  disposed  in  a  definite  order; 
why  this  basis  divides  into  distinct  masses,  cells,  grouped  each 
around  a  distinct  body,  the  nucleus ;  why  chemical  and  physical 
events  take  place  in  a  particular  order  in  each  cell,  the  regulating 
power  being  within  the  cell  itself;  why  senescence  and  rejuvena- 
tion take  place  ;  and  finally  the  sources  of  consciousness,  memory, 
and  habit.  No  mechanical  explanation,  or  theory  of  conscious 
automatism  suffices,  but  a  vital  force  is  the  only  reasonable 
hypothesis;  the  nature  of  that  force  is,  for  the  present,  an  entire 
mystery,  and  before  we  can  expect  to  discover  it  we  must  settle 
what  are  the  phenomena  to  be  explained  by  it. 

[From  the  Proceedings  of  the  American  Association  for  the  Advancement  of 
Science,  vol.  xxviii.,  Saratoga  Meeting,  August,  1879.] 


APPENDIX  VI.     THE  AGE-RECKONER 

IN  making  records  of  growth  it  is  advantageous  to  weigh 
the  animals  at  definite  ages,  using  the  same  ages  in  all  cases. 
As  it  is  somewhat  laborious  to  calculate  the  proper  dates 
for  an  animal  born  on  a  given  day,  the  age-reckoner,  herewith 
figured,  was  devised.  It  does  away  with  all  calculation,  for  after 
setting  the  machine  for  a  given  birth-date,  all  the  dates  on  which 
weighings  are  to  be  made  can  be  read  off  at  once.  The 
apparatus  as  shown  in  the  figure  consists  of  two  metal 
wheels  close  together  on  a  single  axle.  The  rims  of  the  wheels 
are  broad  and  each  one  bears  365  lines,  one  for  each  day 
in  the  year.  The  right-hand  wheel  is  inscribed  with  the  months 
and  days  of  the  month,  for  example,  "  yV<?z;."  marks  November 
ist,  the  numbers  below  November  5th,  15th,  and  25th.  ''''Dec.''' 
marks  December  ist.  This  wheel  which  bears  the  dates  may  be 
called  the  "  calendar  wheel,"  and  is  attached  permanently  upon 
the  axis.  -The  left  or  "'age  wheel"  can  be  revolved  without  turn- 
ing the  axis,  so  that  it  can  be  set  with  its  zero  line  opposite  any 
date  on  the  calendar  wheel;  it  can  then,  by  means  of  the  set  screw 
seen  in  the  figure,  be  clamped  to  the  axle,  and  both  wheels  will 
then  revolve  together.  Upon  the  age  wheel  the  ages  are  marked, 
for  every  ten  days  up  to  210,  thereafter  every  thirty  for  five 
months.  Obviously  after  the  age  wheel  has  been  set  with  its  zero 
at  the  date  of  birth  and  been  clamped,  all  the  ages  selected  for 
weighing  will  fall  opposite  the  proper  dates,  and  may  be  read  off 
by  simply  revolving  the  two  wheels. 

It  was  the  usual  practice  as  soon  as  an  animal  (or  litter)  was 
born  to  set  the  age-reckoner,  and  then  copy  down  from  it  on 

273 


274 


AGE,  GROWTH,  AND  DEATH 


a  sheet  of  paper  all  the  dates  for  weighing  the  animal  during  the 
ensuing  year.     Then  in  a  diary  all  the  animals  of  whatever  sort 


Fig.  73.     Age-reckoner. 

to   be   weighed   were   entered   for   each   day,  thus  reducing  the 
chance  of  omissions. 


INDEX 


Abderhalden,  107 

Ability  and  age,  246 

Acanthias,  181 

Addison  (foot-note),  2 

Adults,  stability  of,  244 

Age.     See  Old  age. 
and  ability,  246 
cause  of  old,  134 
cellular  changes  of,  38 
four  laws  of,  stated,  250 

Age-reckoner,  271 

Allen,  B.  M.,  180 

Altmann,  235 

Amblystomum,  164 

Americans,  size,  247 

Amitosis  (foot-note),  221 

Amoeba,  152 

Animals,  old  age  of,  30 
size  of,  65 

Annelids,  regeneration  in,  212 

Ascidians,  211 

Atrophy  with  age,  22,  23 

Autolysis,  73 

B 

Baby,  psychology  of,  236 

Bache  fund,  grant  from,  92 

Balfour,  F.  M.  (foot-note),  77 

Bees,  31 

Bienstock  (foot-note),  27 

Biophors,  236 

Bizzozero  (foot-note),  192 

Blood  corpuscles,  76,  139 

destruction  of,  36 

shape,  76 
Blood-vessels,  degeneration  of, 
Bombici,  178 
Bone,  61 

and  nerves,  32 

in  old  age,  1 1 


80 


Bouchard,  117 

Bowditch,  H.  P.,  90 

Boys,  table  of  growth  of,  m 

Brain  in  old  age,  17,  33 

of  bees,  31 
Budding  in  annelids,  212 
Butler,  W.  F.  (foot-note),  2 


C 


Calkins,  G.  N.,  230,  262 
Cameron,  W.  (foot-note),  113 
Carp,  longevity  of,  264 
Cartilage,  60 

ossification  of  (foot-note),  81 
Cells,  adult,  49 

complete    differentiation    of, 
219 

cy  le  of,  229 

death  of,  80,  83 

defined,  39 

degeneration  of,  67 

division  of,  42 

embryonic,  47,  48,  135 

four  kinds  of,  218 

highly  differentiated,  219 

illustrated,  132 

multiplication,  44,  134 

number  differentiated,  196 

old,  161 

partial  differentiation  of,  219 

size,  135,  151 

undifferentiated,  135,  152 

young,  importance  of,  213 

young  types,  218 
Cerebellum,  52,  186 
Chevreul,  portrait  of,  6 
Chick  embryos,  growth  of,  118 
Chickens,  growth  of,  loi 

growth  tables,  256 
Child  at  birth,  photograph,  7 
Chromatine,  defined,  41 


275 


276 


INDEX 


Chromosome,  denned,  42 
Cicero,  i 
Ciona,  211 

Circulation  in  old  age,  14,  15 
Compayre  (foot-note),  237 
Connective  tissue,  32,  60 
Cornaro,  2 
Corpuscles,  blood,  76 

salivary  (foot-note),  72 
Councilman,    W.    T.    (foot-note), 

138 
Curtis,  W.  C.  (footnote),  211 
Cycle,  cellular,  229 
Cytomorphosis,  38,  169,  206 

and  longevity,  228 

defined, 46 

of  blood  corpuscles,  76 

three  laws  of,  249 


D 


Darwin,  Charles,  234 

foot-note,  237 
Death,  169,  213,  216,  229 

accompanies  development,  36 

and  differentiation,  215 

natural,  261 

of  cells,  80 
gland,  72 

table  of  (foot-note),  75 
while  young,  74 

of  hair,  36 

of  higher  organisms,  215 

of  lower  organisms,  214 

of  parts,  214 

of  protozoa,  260 
Degeneration  of  cells,  67 

brain  cells,  69 
Deiters  (Fig.  11),  50 
Descartes,  241 

Development,     embryonic     type, 
196 

larval  type,  196 

psychological,  236 
Differentiation,  153,  158,  225 

and  functions  in  man,  216 

and  growth,  161 

complex,  194 

defined,  45,  64 

in  embryos,  158,  160 

in  higher  animals,  195,  196 

in  larvae,  194 

object  of,  154 


of  connective  tissue,  149 

of  gland  cells,   147 

of  muscle,   147 

of  nerve  cells,   144 

of  protoplasm,   143 

of  Stentor,  142 
Digestive  tract  in  old  age,  14 
Dilepta,    184 
Disease,  of  old  age,  23 

two  kinds  of,  224 
Disharmonies,  Metchnikoff  on,  24 
Dog-fish,  181 
Donaldson,  H.  H.,  no,  m,  114 

foot-note,  128 
Driesch,  Hans,  170 
Dungern  and  Werner,  205 
Dysentery,  138 


E 


Earthworms,  198 

Entamoeba,  137 

"  Entdifferenzirung,  "  1 70 

Epithelium,  54 

Exercise,  effect    of  on  muscle,  n 

Eycleshymer,  A.  C,  156,  164.,  i  78 


Face  in  old  age,  4 
Fatigue,  mental,  245 
Fermentation  in  intestine,  25 
Fibrils  of  connective  tissue,  43 
Fischer  (foot-note),  27 
Fraisse  (foot-note),  204 


Gait  in  old  age,  5 
Gemmules,  234,  235 
Genetic  restriction,  222 
Gerassimow,  J.  J.,  184 
Germ  cells,  181 

in  old  age,  16 
Germ  layers  (foot-note),  47 
Girls,  table  of  growth  of,  112 
Gland-cells,  56 
Glands,  growth  of,  192 

orbital,  56,  147 
Goeze  (foot-note),  197 
Gould,  B.  A.,  92,  247 

on  stature  of  soldiers,  xiii 
Growth  {see  also  Rate  of  growth) 


INDEX 


277 


Growth — Continued 

and  diiierentiation,   161 

appositional,  igi 

boys,  table  of,  1 1 1 

cause  of  loss  of,  161 

centres  of,  186,  188 

chick  embryos,  118 

dififuse,  189 

early  rapid  decline,  130,  131 

errors  in  statistics,  xii— xiii 

experiments  on,  x-xii 

focal,  igi 

girls,  table  of,   112 

interstitial,  189 

loss  in. rate  at  birth,  126 

man,  before  birth,  128 

method  of  study,  xi-xiii 

of  Boston  children,  90 

of  glands,  192 

of  hairs,  192 

of  lens,  191 

of  tumours,  206,  224 

of  young  cells,  186 

power  at  birth,  126 

prepubertal  acceleration,  xii 

rapidity  of,  90 

rate  of,  86 

decline  before  birth  126, 
"  129 

defined,  93 

influence  of  temperature, 

88 
method  of  measuring,  86 

regulation  of,  186,  205 

relation    to    composition    of 
milk,    107 
Growth-zones,  192 
Gruber,  141 ,  200 
Guinea-pigs,  experiments  with,  89 

selected   for  growth    experi- 
ments, X 


H 


Haacke,  235 

Haeckel,  234 

Haemoglobin,  78 

Hair,  death  of,  36 

differentiation,  59 
growth  of,  192 
origin  of  white,  27 
pigment  of,  36,  82 

Handmann,  E.  (foot-note),  17 


Hardesty,  I.  (foot-note),  67 
Hartmann,  M.,  263 
Hatai,  i  78 
Heart  in  old  age,  14 

isolated,  214 
Heat  of  body,  19 
Heiberg,  K.  A.,  184 
Herbst,  C,  210 
Hertwig,  O.,  88 
Hertwig,  R.  (foot-note),  129,  184 

263 
Hodge,  C.  F.,  69 
Hogan,  Louise  (foot-note),  237 
Holmes,  O.  W.,  i 
Honey  bees,  31 
Hubrecht,  174 

Humphry,  G.  M.  (foot-note),  10 
Hyaloplasma,  42 
Hyatt,  A.,  225 
Hypertrophy  of  cells,  71 


Ids,  236 

Index,  mitotic,  220 
Inhibition,  205 
Insects,  old  age  of,  31 
Intestinal  fermentation,  25 
glands,  192 


Jackson,  R.  T.,  226 
Jaw  in  old  age,  10 

K 

Keibel,  Franz  (Fig.  42),  119 

(Fig.  43).  121 
Keller,  J.  (foot-note),  211 
Kidneys,  80 

degeneration  of,  80,  81 
Kieffer,  J.  (foot-note),  10 
Kolliker,  A.   (foot-note),  146 
Korschelt,  E.,  i  70 
Kronthal,  170 
Kussmaul  (foot-note),  237 


Lache,  178 
Lactic  acid,  27 
Laws  of  age,  250 

of  cytomorphosis,  249 


278 


INDEX 


Learning,  power  of,  in  adults  243 

m  children,  243 
Leaves,  old,  35 
Lens  of  eye,  190 

growth,  191 

regenerated  from  retina,  223 
Leucocytes  form  nerve  cells,  170 
Levene,  P.  A.  (foot-note),  73 
Levi,  G.   (foot-note),  65 
Lewis,  F.  T.  (foot-note),  77 
Life,  prolongation  of,  248 

theory  of,  viii,  265 
Life-units,  233 
Liver,  33 

struggle    against    connective 
tissue,  33 
Loeb,  J.,  211 
Longevity,  23,  226 

of  animals,  264 
Lucas,  F.  A.,  264 
Ludwig,  Carl,  referred  to,  iii 
Lungs  in  old  age,  14 


M 


Malaria,  139 
Mandible  in  old  age,  10 
Marinesco,  178 
Martelly  (foot-note),  27 
Maupas,  E.,  262 
Memory  in  old  age,  5 
Metchnikoff,  22,  24,  27,  28,  74 
Milk,  relation  to  growth,   107 

sour,  28 
Mind  in  old  age,  5 
Mmgazzini,  Pio,  211 
Minot,  Charles   S.,  investigations 
reviewed,  v-ix 

point  of  view,  vii 

theory  of  life,  265 
Mitotic  index,  220 
Montgomery,  T.  H.  (foot-note),  26 
Moore,  Kathleen   (foot-note),  237 
Morpurgo,  B.,  11 
Moseley  (foot-note),  211 
Mosso,  letter  to,  iii 
Miihlmann,  28,  109,  113 

foot-note,  no,  128 

Fig.  45.  127 
Miiller,  O.  F.,  212 
Muscles  in  old  age,  1 1 


Muscle  fibres,   differentiation,   62 

growth  of,  157 

striated,  63 
Muscular  segment,  primitive,  220 


N 


Nageli,  235 

Nauwerck   (foot-note),   204 

Necrobiosis,  defined,  71 

Necturus,  156 

Nerve  cells,  adult  (Fig.  13),  53 

cerebellar  (Fig.  12),  51,  187 

motor,  50 

origin  from  leucocytes,  i  70 
Nerves  and  bone,  32 
Neurones,  200 
Notochord,  80 
Nuclei  cause  rejuvenation,  166 

differentiation  of,  175 

relative  increase,  156,  166 

size  of,  184 

size  reduced,  i  79 
Nucleus  defined,  41 

growth  of,  relative,  161 

illustrated,  132 

in  secretion,  57 
Nussbaum,  M.,  180,  222,  235 


O 


Old  age  and  anatomical  quality, 

34 
and  organic  structure,  34 
as  a  disease,  23 
cause  of,  134 
defined,  84 
general  changes,  21 
in  animals,  30 
in  plants,  34 

medical  theories  of,  22-30 
most  marked  in  high  animals, 

34 
period   of   slowest  decline,  5, 

85 
Olmer,  i  78 
Oniscus,  207 

Oppenheim  (foot-note),  237 
Organic  structure  and  age,  34 
Organs,  over-living,  214 
Osier,  23,  245 
Ost,  J.,  207 
Ovum,  growth  until  birth,  129 


INDEX 


279 


Ovum — Contimied 

human,  weight,  128 

volume,  130 
segmentation    of,    162,     163, 
171.   172,    173 


Pancreas,  57,  148 

Pangenesis,  234 

Phagocytes,  26,  74 

Physiological  units,  234 

"  Pill-bug,  "  207 

Planarians,  210 

Planorbis,  172 

Plants,  old  age  in,  34 

Plasmodium,  139 

Polyps,  197 

Porter,  W.  T.  (foot-note),  15 

Prevost   and   Dumas   (foot-note), 

172 
Preyer,  Wm.  (foot-note),  237 
Protoplasm  defined,  41 

differentiation  of,  143 

illustrated  132 

increase  of,  134 

with  age,  156,  157 

problem  of  its  increase,  iv 
Psfiudopodia,  138 
Pulse,  changes  with  age,  15 

in  old  age,  18 


Quetelet,  109 


Q 


R 


Rabbits,  condition  at  birth,  104 
embryos,  135 

growth  of,  122 
percentage     increments, 

124 
weight  of,  124 
growth  of,  102 
growth  tables,  251 
Rabl,  Carl  (foot-note),  172 
Rand,  Benj.  (foot-note),   236 
Rate  of  growth,  86 
defined,  93 
in  chickens,  loi 
in  guinea-pigs,  94 
in  man,  98,  106,  108 


in  rabbits,  102 

method  of  representing,  96 
Reditferentiation,  170 
Regeneration,  169,  197 

in  annelids,  212 

in  ascidians,  211 

in  Ciona,  211 

in  planarians,  210 

in  polyps,  197 

in  salamanders,  198 

in  Stentor,  199 

in  tadpoles,  198 

of  antenna,  207 

of  eye  stalks,  210 

of  lens  from  retina,  223 

of  muscle,  201 

of  nerve  fibres,  200 

of  skin,  204 
Regulation  of  growth,  205 
Rejuvenation  caused    by    nuclei, 
166 

perpetuation  of,  180 

theory  of,  166 
Remy  Collin,  178 
Repair  in  old  age,  20 
Respiration  in  old  age,  18 
Retina,  64 

Roberts  (foot-note),   112 
Rovighi,  A.  (foot-note),  27 
Rubaschkin,  W.    (foot-note),   181 


Salamander,  156 

regeneration  in,  198 
Salivary  corpuscles  (foot-note),  72 
Schaper   and    Cohen    (foot-note), 

191 
Schmincke  (foot-note),  204 
Schultze,  L.  S.,  211 
Schwann,  Theodor,  39 
Sclerosis,  15,  30 
Seals,  longevity  of,  264 
Segment,  primitive  muscular,  220 
Semper,  Carl,  212 
Senescence,  132,  167 

a  vital  phenomenon,  x 

Hyatt's  study  of,  225 

in  protozoa,  231 
Sex  cells,  181 

Shinn,  M.  W.  (foot-note),  237,  239 
Size  of  animals,  65 

of  cells,  135,  151 


INDEX 


Size — Continued 

of  nerve  cells,  67 
Skeleton  in  old  age,  10 
Skin,  death  of,  36,  71 
Sobotta,  145 
Soldiers,  stature  of,  xiii 
Spallanzani,  197 

foot-note,  198 
Specification  defined,  45 
Spencer,  Herbert,  234 
Spinal  cord,  embryonic,  50 
Spirogyra,  184 
Stature  decreases  with  age,  2 

of  Germans,  2 

of  soldiers,  xiii 
Steele,  M.  I.,  210 
Stentor,  141,  142,  199 
Stevens,  Miss  (foot-note),  211 
Stomach,  self-digestion,  72 
Struggles  of  tissues,  32 
Syncytium,  43,  150 

in  embryos,  44 


Tadpoles,  growth  of,  88 

regeneration  in,  198 

tails  of,  83 
Tails  of  tadpoles,  83 
Tanner,  Amy  E.   (foot-note),   237 
Tarsius,  162 
Teeth,  82 

Teleological  mechanism,  20 
Temperature    influences    growth, 

88 
Theory    of    germinal    continuity, 
183 


of  life,  viii,  265     •• 
Thoma,  115,  116 
Thymus,  82 
Tigroid  substance,  54 
Tissier  (foot-note),  27 
Tissues,  struggles  of,  32 
Tortoises,  longevity  of,  264 
Trembley,  197,  198 
Trypanosoma,  140 
Tumours,  206 

growth  of,  224 

V 

Variation  and  ability,  246 
Vertebral  column  in  old  age,  2 
Vital  force,  vii,  viii 
Volkmann  (foot-note),  204 

W 

Waldeyer  (foot-note),  203 
Weidenreich  (foot-note),  76,  77,  79 
Weismann,  A.  (foot-note),  226 

on  life  units,  235 
Whales,  longevity  of,   264 
Whitman,  235 
Woods,  F.  A.,  180 

Y 

Yolk  granules,  195 
Z 

Ziegler,  Ernst,  figure  after,  202 
foot-note,  204 


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23 — Mosquito  Life.  The  Habits  and  Life  Cycles  of  the  Known  Mos- 
quitoes of  the  United  States  ;  Methods  for  their  Control  ;  and  Keys  for 
Easy  Identification  of  the  Species  in  their  various  Stages.  An  account 
based  on  the  Investigation  of  the  Late  James  William  Dupree,  Surgeon- 
General  of  Louisiana,  and  upon  the  original  observations  by  the  Writer. 
By  Evelyn  Groesbeeck  Mitchell,  A.B.,  M.S.  With  64  Illustra- 
tions.    Crown  8vo.     Net,  $2.00. 

This  volume  has  been  designed  to  meet  the  demand  of  the  constantly  increasing 
number  of  students  for  a  work  presenting  in  compact  form  the  essential  facts  so  far  made 
known  by  scientific  investigation  in  regard  to  the  different  phases  of  this,  as  is  now  con- 
ceded, important  and  highly  interesting  subject.  While  aiming  to  keep  within  reasonable 
bounds,  that  it  may  be  used  for  work  in  the  field  and  in  the  laboratory,  no  portion  of  the 
work  has  been  slighted,  or  fundamental  information  omitted,  in  the  endeavor  to  carry 
this  plan  into  effect. 

24. — Thinking,  Feeling,  Doing.  An  Introduction  to  Mental  Science. 
By  E.  W.  Scripture,  Ph.D.,  M.D.,  Assistant  Neurologist  Columbia 
University,  formerly  Director  of  the  Psychological  Laboratory  at  Yale 
University.  i8g  Illustrations.  2d  Edition,  Revised  and  Enlarged. 
Crown  Svo.     Net,  $1.75. 

"  The  chapters  on  Time  and  Action,  Reaction  Time,  Thinking  Time,  Rhythmic  Action, 
and  Power  and  Will  are  most  interesting.  This  book  should  be  carefully  read  by  every 
one  who  desires  to  be  familiar  with  the  advances  made  in  the  study  of  the  mind,  which 
advances,  in  the  last  twenty-five  years,  have  been  quite  as  striking  and  epoch  making  as 
the  strides  made  in  the  more  material  lines  of  knowledge." — Jour.  Amer.  Med.  Ass'n, 
Feb.  22,  1908. 

In  preparation: 

The  Invisible  Spectrum.  By  Professor  C.  E.  Mendenhall,  University 
of  Wisconsin. 

The  Physiology  and  Hygiene  of  Exercise.  By  Dr.  G.  L.  Meylan, 
Columbia  University. 

Other  volumes  to  be  announced  later. 


■2? 


The  Science  Series 


Edited  by  Edward  Lee  Thorndike,  Ph.D.,  Columbia  Uni 

versity,  with  the  cooperation  of  Frank  Evers  Beddard, 
F.R.S.,  in  Great  Britain. 

Each  volume  of  the  series  treats  of  some  department  of 
science  with  reference  to  the  most  recent  advances,  and 
is  contributed  by  an  author  of  acknowledged  authority. 
Every  effort  is  made  to  maintain  the  standard  set  by  the 
first  volumes,  until  the  series  shall  represent  the  more  im- 
portant aspects  of  contemporary  science.  The  advance  of 
science  has  been  so  rapid,  and  its  place  in  modern  life  has 
become  so  dominant,  that  it  is  needful  to  revise  continually 
the  statement  of  its  results,  and  to  put  these  in  a  form  that  is 
intelligible  and  attractive.  The  man  of  science  can  himself 
be  a  specialist  in  one  department  only,  yet  it  is  necessary  for 
him  to  keep  abreast  of  scientific  progress  in  many  directions. 
The  results  of  modern  science  are  of  use  in  nearly  every  pro- 
fession and  calling,  and  are  an  essential  part  of  modern 
education  and  culture.  A  series  of  scientific  books,  such  as 
has  been  planned,  should  be  assured  of  a  wide  circulation, 
and  should  contribute  greatly  to  the  advance  and  diffusion  of 
scientific  knowledge. 

The  volumes  are  issued  in  octavo  form,  and  are  fully  illus- 
trated in  so  far  as  the  subject-matter  calls  for  illustrations. 


G.  P.  PUTNAM'S  SONS,  New  York  &  London 


THE  SCIENCE  SERIES 


Edited  by  Edv/ard  Lee  Thorndike,  Ph.D.,  and 
F.  E.  Beddard,  M.A.,  F.R.S. 


I. — The  Study  of  Man.  By  Professor  A.  C.  Haddon,  M.A.,  D.Sc, 
M.R.I. A.     Fully  illustrated.     8°,  $2.00. 

"A  timely  and  useful  volume.  .  .  .  The  author  wields  a  pleasing  pen  and  knows 
how  to  make  the  subject  attractive.  .  .  .  The  work  is  calculated  to  spread  among  its 
readers  an  attraction  to  the  science  of  anthropology.  The  author's  observations  are 
exceedingly  genuine  and  his  descriptions  are  vivid." — London  AthencEutn. 

2. — The  Groundwork  of  Science.  A  Study  of  Epistemology.  By 
St.  George  Mivart,  F.R.S.     8°,  $1  75. 

"  The  book  is  cleverly  written  and  is  one  of  the  best  works  of  its  kind  ever  put  before 
the  public.  It  will  be  interesting  to  all  readers,  and  especially  to  those  interested  in  the 
study  of  science." — New  Haven  Leader. 

3. — Rivers  of  North  America.  A  Reading  Lesson  for  Students  of  Geo- 
graphy and  Geology.  By  Israel  C.  Russell,  Professor  of  Geology, 
University  of  Michigan,  author  of  "  Lakes  of  North  America,"  "  Gla- 
ciers of  North  America,"  "  Volcanoes  of  North  America,"  etc.  Fully 
illustrated.     8°,  $2.00. 

"There  has  not  been  in  the  last  few  years  until  the  present  book  any  authoritative, 
broad  resume  on  the  subject,  modified  and  deepened  as  it  has  been  by  modern  research 
and  reflection,  which  is  couched  in  language  suitable  for  the  multitude.  .  .  .  The  text 
is  as  entertaining  as  it  is  instructive." — Boston  Tra7iscript. 

4. — Earth  Sculpture ;  or,  The  Origin  of   Land-Forms.      By  James 
Geikie,  LL.D.,  D.C.L.,  F.R.S.,  etc.,  Murchison  Professor  of  Geology 
and    Mineralogy  in   the  University   of   Edinburgh  ;   author   of   "  The 
Great  Ice  Age,"  etc.     Fully  illustrated.     8°,  $2.00. 
"  This  volume  is  the  best  popular  and  yet  scientific  treatment  we  know  of  of  the  ori- 
gin and  development  of  land-forms,  and  we  immediately  adopted  it  as  the  best  available 
text-book  for  a  college  course  in  physiography.    .    .    .    The  book  is  full  of  life  and  vigotf 
and  shows  the  sympathetic  touch  of  a  man  deeply  in  love  with  nature." — Science. 

5. — Volcanoes.     By  T.  G.  Bonney,  F.R.S.,  University  College,  London. 
Fully  illustrated.     8°,  $2.00. 
"  It  is  not  only  a  fine  piece  of  work  from  a  scientific  point  of  view,  but  it  is  uncom- 
monly attractive  to  the  general  reader,  and  is  likely  to  have  a  larger  sale  than  most  books 
of  its  class." — Springfield  Republican. 

6. — Bacteria  :  Especially  as  they  are  related  to  the  economy  of  nature,  to 
industrial  processes,  and  to  the  public  health.  By  George  Newman, 
M.D.,  F.R.S.  (Edin.),  D.P.H.  (Camb.),  etc..  Demonstrator  of  Bac- 
teriology in  King's  College,  London.  With  24  micro-photographs  of 
actual  organisms  and  over  70  other  illustrations.     8°,  $2.00. 

'■'Dr.  Newman's  discussions  of  bacteria  and  disease,  of  immunity,  of  antitoxins,  and 
of  methods  of  disinfection,  are  illuminating,  and  are  to  be  commended  to  all  seeking  in- 
formation on  these  points.  Any  discussion  of  bacteria  will  seem  technical  to  the  uniniti- 
ated, but  all  such  will  find  in  this  book  popular  treatment  and  scientific  accuracy  happily 
combined."—  The  Dial.  rj 


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